Skip to main content
SpringerLink
Log in

Enhancement of the Radiation Response with Interleukins and Interferons

  • Chapter
Modification of Radiation Response

Part of the book series: Medical Radiology ((Med Radiol Radiat Oncol))

  • 143 Accesses

Abstract

Physical and technical developments and refinements of the last decade in radiation oncology have been impressive. Particle therapy is on the rise again, and photon therapy has received a major boost from intensity modulation, making delivery of tumor-conformal radiation treatment easier than ever before. Intensity-modulated particle therapy, regarded by some as the holy grail of radiotherapy, is on the horizon, combining highly conformal dose distributions with low integral doses. However, while any desired dose distribution can be created now or in a not too distant future, this does not solve the problem of normal tissue present within the irradiated target volumes due to infiltration by the tumor. Therefore, further progress can only be expected from efforts directed at widening the therapeutic window between tumors and normal tissue through specific modulation of their responses to radiotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 16.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abbas AK, Murphy KM, Sher A (1996) Functional diversity of helper T lymphocytes. Nature 383:787–793

    PubMed  CAS  Google Scholar 

  • Abbas AK, Lichtman AH, Pober JS (2001) Cellular and molecular immunology. Saunders, Philadelphia

    Google Scholar 

  • Abdulkarim B, Sabri S, Deutsch E, Vaganay S, Marangoni E, Vainchenker W, Bongrand P, Busson P, Bourhis J (2000) Radiation-induced expression of functional Fas ligand in EBV-positive human nasopharyngeal carcinoma cells. Int J Cancer 86:229–237

    PubMed  CAS  Google Scholar 

  • Addison CL, Bramson JL, Hitt MM, Muller WJ, Gauldie J, Graham FL (1998) Intratumoral coinjection of adenoviral vectors expressing IL-2 and IL-12 results in enhanced frequency of regression of injected and untreated distal tumors. Gene Ther 5:1400–1409

    PubMed  CAS  Google Scholar 

  • Akbari O, DeKruyff RH, Umetsu DT (2001) Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nat Immunol 2: 725–731

    PubMed  CAS  Google Scholar 

  • Albert ML, Sauter B, Bhardwaj N (1998) Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392:86–89

    PubMed  CAS  Google Scholar 

  • Angioli R, Sevin BU, Perras JP, Untch M, Hightower RD, Nguyen HN, Steren A, Villani C, Averette HE (1992) Rationale of combining radiation and interferon for the treatment of cervical cancer. Oncology 49:445–449

    PubMed  CAS  Google Scholar 

  • Angioli R, Sevin BU, Perras JP, Untch M, Koechli OR, Nguyen HN, Steren A, Schwade JG, Villani C, Averette HE (1993) In vitro potentiation of radiation cytotoxicity by recombinant interferons in cervical cancer cell lines. Cancer 71: 3717–3725

    PubMed  CAS  Google Scholar 

  • Arai H, Gordon D, Nabel EG, Nabel GJ(1997) Gene transfer of Fas ligand induces tumor regression in vivo. Proc Natl Acad Sci U S A 94:13862–13867

    PubMed  CAS  Google Scholar 

  • Atkins MB, Robertson MJ, Gordon M, Lotze MT, DeCoste M, DuBois JS, Ritz J, Sandler AB, Edington HD, Garzone PD, Mier JW, Canning CM, Battiato L, Tahara H, Sherman ML (1997) Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies. Clin Cancer Res 3:409–417

    PubMed  CAS  Google Scholar 

  • Atzpodien J, Kirchner H, Hanninen EL, Deckert M, Fenner M, Poliwoda H (1993) Interleukin-2 in combination with interferon-alpha and 5-fluorouracil for metastatic renal cell cancer. Eur J Cancer 29A[Suppl 5]:S6–S8

    PubMed  Google Scholar 

  • Atzpodien J, Neuber K, Kamanabrou D, Fluck M, Brocker EB, Neumann C, Runger TM, Schuler G, von den Driesch P, Muller I, Paul E, Patzelt T, Reitz M (2002) Combination chemotherapy with or without s.c. IL-2 and IFN-alpha: results of a prospectively randomized trial of the Cooperative Advanced Malignant Melanoma Chemoimmunotherapy Group (ACIMM). Br J Cancer 86:179–184

    PubMed  CAS  Google Scholar 

  • Barbera N, Palmucci T, Chiarenza A, Bartoloni G, Cordaro S, Greco S, Scapagnini U, Bernardini R (1993) Radioprotective effects of the association thymopentin-interleukin-1 alpha in the C57BL/6 mouse. Pharmacol Toxicol 72:256–261

    PubMed  CAS  Google Scholar 

  • Belka C, Ottinger H, Kreuzfelder E, Weinmann M, Lindemann M, Lepple-Wienhues A, Budach W, Grosse-Wilde H, Bamberg M (1999) Impact of localized radiotherapy on blood immune cell counts and function in humans. Radiother Oncol 50:199–204

    PubMed  CAS  Google Scholar 

  • Bendelac A, Medzhitov R (2002) Adjuvants of immunity: harnessing innate immunity to promote adaptive immunity. J Exp Med 195:F19–F23

    PubMed  CAS  Google Scholar 

  • Bogdan C, Paik J, Vodovotz Y, Nathan C (1992) Contrasting mechanisms for suppression of macrophage cytokine release by transforming growth factor-beta and interleukin-10. J Biol Chem 267:23301–23308

    PubMed  CAS  Google Scholar 

  • Bradley JD, Scott CB, Paris KJ, Demas WF, Machtay M, Komaki R, Movsas B, Rubin P, Sause WT (2002) A phase III comparison of radiation therapy with or without recombinant beta-interferon for poor-risk patients with locally advanced non-small-cell lung cancer (RTOG 93-04). Int J Radiat Oncol Biol Phys 52:1173–1179

    PubMed  CAS  Google Scholar 

  • Braunschweiger PG, Basrur V, Santos O, Adessa A, Houdek P, Markoe AM (1996) Radioresistance in murine solid tumors induced by interleukin-1. Radiat Res 145:150–156

    PubMed  CAS  Google Scholar 

  • Brinkmann OA, Bruns F, Prott FJ, Hertle L (1999) Possible synergy of radiotherapy and chemo-immunotherapy in metastatic renal cell carcinoma (RCC). Anticancer Res 19: 1583–1587

    PubMed  CAS  Google Scholar 

  • Brunda MJ, Luistro L, Warrier RR, Wright RB, Hubbard BR, Murphy M, Wolf SF, Gately MK (1993) Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J Exp Med 178:1223–1230

    PubMed  CAS  Google Scholar 

  • Buckner JC, Schomberg PJ, McGinnis WL, Cascino TL, Scheithauer BW, O’Fallon JR, Morton RF, Kuross SA, Mailliard JA, Hatfield AK, Cole JT, Steen PD, Bernath AM (2001) A phase III study of radiation therapy plus carmustine with or without recombinant interferon-alpha in the treatment of patients with newly diagnosed high-grade glioma. Cancer 92:420–433

    PubMed  CAS  Google Scholar 

  • Cameron RB, Spiess PJ, Rosenberg SA (1990) Synergistic antitumor activity of tumor-infiltrating lymphocytes, interleukin 2, and local tumor irradiation. Studies on the mechanism of action. J Exp Med 171:249–263

    PubMed  CAS  Google Scholar 

  • Chang AY, Keng PC (1987) Potentiation of radiation cytotoxicity by recombinant interferons, a phenomenon associated with increased blockage at the G2-M phase of the cell cycle. Cancer Res 47:4338–4341

    PubMed  CAS  Google Scholar 

  • Chappell DB, Zaks TZ, Rosenberg SA, Restifo NP (1999) Human melanoma cells do not express Fas (Apo-1/CD95) ligand. Cancer Res 59:59–62

    PubMed  CAS  Google Scholar 

  • Chen L, McGowan P, Ashe S, Johnston J, Li Y, Hellstrom I, Hellstrom KE (1994) Tumor immunogenicity determines the effect of B7 costimulation on T cell-mediated tumor immunity. J Exp Med 179:523–532

    PubMed  CAS  Google Scholar 

  • Chiang CS, Hong JH, Wu YC, McBride WH, Dougherty GJ (2000) Combining radiation therapy with interleukin-3 gene immunotherapy. Cancer Gene Ther 7:1172–1178

    PubMed  CAS  Google Scholar 

  • Clerici M, Shearer GM, Clerici E (1998) Cytokine dysregulation in invasive cervical carcinoma and other human neoplasias: time to consider the TH1/TH2 paradigm. J Natl Cancer Inst 90:261–263

    PubMed  CAS  Google Scholar 

  • Cole S, Lewkowicz SJ, Townsend KM (1984) Langerhans cell number and morphology in mouse footpad epidermis after X irradiation. Radiat Res 100:594–606

    PubMed  CAS  Google Scholar 

  • Connors JM, Andiman WA, Howarth CB, Liu E, Merigan TC, Savage ME, Jacobs C (1985) Treatment of nasopharyngeal carcinoma with human leukocyte interferon. J Clin Oncol 3:813–817

    PubMed  CAS  Google Scholar 

  • Coughlin CM, Salhany KE, Wysocka M, Aruga E, Kurzawa H, Chang AE, Hunter CA, Fox JC, Trinchieri G, Lee WMF (1998) Interleukin-12 and interleukin-18 synergistically induce murine tumor regression which involves inhibition of angiogenesis. J Clin Invest 101:1441–1452

    PubMed  CAS  Google Scholar 

  • Coulie PG, Ikeda H, Baurain JF, Chiari R (1999) Antitumor immunity at work in a melanoma patient. Adv Cancer Res 76:213–242

    PubMed  CAS  Google Scholar 

  • DeKruyff RH, Fang Y, Umetsu DT (1995) IL-4-based helper activity of CD4+ T cells is radiation sensitive. Cell Immunol 160:248–256

    PubMed  CAS  Google Scholar 

  • DeLaney TF, Afridi N, Taghian AG, Sanders DA, Fuleihan NS, Faller DV, Nogueira CP (1996) 13-cis-retinoic acid with alpha-2a-interferon enhances radiation cytotoxicity in head and neck squamous cell carcinoma in vitro. Cancer Res 56:2277–2280

    PubMed  CAS  Google Scholar 

  • Dieckmann D, Plottner H, Berchtold S, Berger T, Schuler G (2001) Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood. J Exp Med 193:1303–1310

    PubMed  CAS  Google Scholar 

  • Dighe AS, Richards E, Old LJ, Schreiber RD (1994) Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN gamma receptors. Immunity 1:447–456

    PubMed  CAS  Google Scholar 

  • Dillman RO, Wiemann M, Oldham RK, Soori G, Bury M, Hafer R, Church C, DePriest C (1995) Interferon alpha-2a and external beam radiotherapy in the initial management of patients with glioma: a pilot study of the National Biotherapy Study Group. Cancer Biother 10:265–271

    PubMed  CAS  Google Scholar 

  • Dillman RO, Shea WM, Tai DF, Mahdavi K, Barth NM, Kharkar BR, Poor MM, Church CK, DePriest C (2001) Interferon-alpha2a and 13-cis-retinoic acid with radiation treatment for high-grade glioma. Neurooncology 3:35–41

    CAS  Google Scholar 

  • Dorie MJ, Allison AC, Zaghloul MS, Kallman RF (1989) Interleukin 1 protects against the lethal effects of irradiation of mice but has no effect on tumors in the same animals. Proc Soc Exp Biol Med 191:23–29

    PubMed  CAS  Google Scholar 

  • Dorie MJ, Kallman RF, Cebulska-Wasilewska A (1991) Interleukin-1 modification of the effects of cyclophosphamide and fractionated irradiation. Int J Radiat Oncol Biol Phys 20:311–314

    PubMed  CAS  Google Scholar 

  • Down JD, Awwad M, Kurilla-Mahon B, Moran K, Ericsson T, Oldmixon B, Lachance A, Watts A, Treter S, Nash K, Gojo S, Sachs DH, White-Scharf ME, Cooper DK (2000) Increases in autologous hematopoietic progenitors in the blood of baboons following irradiation and treatment with porcine stem cell factor and interleukin-3. Transplant Proc 32: 1045–1046

    PubMed  CAS  Google Scholar 

  • Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, Jackson V, Hamada H, Pardoll D, Mulligan RC (1993) Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting antitumor immunity. Proc Natl Acad Sci U S A 90:3539–3543

    PubMed  CAS  Google Scholar 

  • Dunst J, Hansgen G, Lautenschlager C, Fuchsel G, Becker A (1999) Oxygenation of cervical cancers during radiotherapy and radiotherapy + cis-retinoic acid/interferon. Int J Radiat Oncol Biol Phys 43:367–373

    PubMed  CAS  Google Scholar 

  • Everson MP, Spalding DM, Koopman WJ (1989) Exquisite sensitivity of dendritic cells to ultraviolet radiation and temperature changes. Transplantation 48:666–671

    PubMed  CAS  Google Scholar 

  • Faris M, Latinis KM, Kempiak SJ, Koretzky GA, Nel A (1998) Stress-induced Fas ligand expression in T cells is mediated through a MEK kinase 1-regulated response element in the Fas ligand promoter. Mol Cell Biol 18:5414–5424

    PubMed  CAS  Google Scholar 

  • Farkkila M, Jaaskelainen J, Kallio M, Blomstedt G, Raininko R, Virkkunen P, Paetau A, Sarelin H, Mantyla M (1994) Randomised, controlled study of intratumoral recombinant gamma-interferon treatment in newly diagnosed glioblastoma. Br J Cancer 70:138–141

    PubMed  CAS  Google Scholar 

  • Fernandez NC, Levraud JP, Haddada H, Perricaudet M, Kourilsky P (1999) High frequency of specific CD8+ T cells in the tumor and blood is associated with efficient local IL-12 gene therapy of cancer. J Immunol 162:609–617

    PubMed  CAS  Google Scholar 

  • Gabrilovich DI, Ciernik IF, Carbone DP (1996) Dendritic cells in antitumor immune responses. I. Defective antigen presentation in tumor-bearing hosts. Cell Immunol 170: 101–110

    PubMed  CAS  Google Scholar 

  • Gambotto A, Tuting T, McVey DL, Kovesdi I, Tahara H, Lotze MT, Robbins PD (1999) Induction of antitumor immunity by direct intratumoral injection of a recombinant adenovirus vector expressing interleukin-12. Cancer Gene Ther 6:45–53

    PubMed  CAS  Google Scholar 

  • Gardner RV (1998) Interferon-gamma (IFN-gamma) as a potential radio-and chemo-protectant. Am J Hematol 58: 218–223

    PubMed  CAS  Google Scholar 

  • Geldhof AB, Moser M, Lespagnard L, Thielemans K, De Baetselier P (1998) Interleukin-12-activated natural killer cells recognize B7 costimulatory molecules on tumor cells and autologous dendritic cells. Blood 91:196–206

    PubMed  CAS  Google Scholar 

  • Gould MN, Kakria RC, Olson S, Borden EC (1984) Radiosensitization of human bronchogenic carcinoma cells by interferon beta. J Interferon Res 4:123–128

    PubMed  CAS  Google Scholar 

  • Gratas C, Tohma Y, Barnas C, Taniere P, Hainaut P, Ohgaki H (1998) Up-regulation of Fas (APO-1/CD95) ligand and down-regulation of Fas expression in human esophageal cancer. Cancer Res 58:2057–2062

    PubMed  CAS  Google Scholar 

  • Hahne M, Rimoldi D, Schroter M, Romero P, Schreier M, French LE, Schneider P, Bornand T, Fontana A, Lienard D, Cerottini J, Tschopp J (1996) Melanoma cell expression of Fas(Apo-1/CD95) ligand: implications for tumor immune escape. Science 274:1363–1366

    PubMed  CAS  Google Scholar 

  • Halin C, Rondini S, Nilsson F, Berndt A, Kosmehl H, Zardi L, Neri D (2002) Enhancement of the antitumor activity of interleukin-12 by targeted delivery to neovasculature. Nat Biotechnol 20:264–269

    PubMed  CAS  Google Scholar 

  • Hareyama M, Imai K, Oouchi A, Takahashi H, Hinoda Y, Tsujisaki M, Adachi M, Shonai T, Sakata K, Morita K (1998) The effect of radiation on the expression of intercellular adhesion molecule-1 of human adenocarcinoma cells. Int J Radiat Oncol Biol Phys 40:691–696

    PubMed  CAS  Google Scholar 

  • Hashimoto S, Shirato H, Hosokawa M, Nishioka T, Kuramitsu Y, Matushita K, Kobayashi M, Miyasaka K (1999) The suppression of metastases and the change in host immune response after low-dose total-body irradiation in tumor-bearing rats. Radiat Res 151:717–724

    PubMed  CAS  Google Scholar 

  • Hazard LJ, Sause WT, Noyes RD (2002) Combined adjuvant radiation and interferon-alpha 2B therapy in high-risk melanoma patients: the potential for increased radiation toxicity. Int J Radiat Oncol Biol Phys 52:796–800

    PubMed  CAS  Google Scholar 

  • Hestdal K, Jacobsen SE, Ruscetti FW, Dubois CM, Longo DL, Chizzonite R, Oppenheim JJ, Keller JR (1992) In vivo effect of interleukin-1 alpha on hematopoiesis: role of colony-stimulating factor receptor modulation. Blood 80: 2486–2494

    PubMed  CAS  Google Scholar 

  • Hillman GG, Younes E, Visscher D, Ali E, Lam JS, Montecillo E, Pontes JE, Haas GP, Puri RK (1995) Systemic treatment with interleukin-4 induces regression of pulmonary metastases in a murine renal cell carcinoma model. Cell Immunol 160: 257–263

    PubMed  CAS  Google Scholar 

  • Hillman GG, Maughan RL, Grignon DJ, Yudelev M, Rubio J, Tekyi-Mensah S, Layer A, Che M, Forman JD (2001) Neutron or photon irradiation for prostate tumors: enhancement of cytokine therapy in a metastatic tumor model. Clin Cancer Res 7:136–144

    PubMed  CAS  Google Scholar 

  • Hodge DL, Martinez A, Julias JG, Taylor LS, Young HA (2002) Regulation of nuclear gamma interferon gene expression by interleukin 12 (IL-12) and IL-2 represents a novel form of posttranscriptional control. Mol Cell Biol 22:1742–1753

    PubMed  CAS  Google Scholar 

  • Hoffmann W, Schiebe M, Hirnle P, Souchon R, Clemens M, Adamietz I, Bamberg M (1997) 13-cis retinoic acid and interferon-alpha +/-irradiation in the treatment of squamous-cell carcinomas. Int J Cancer 70:475–477

    PubMed  CAS  Google Scholar 

  • Hoffmann W, Blase MA, Santo-Hoeltje L, Herskind C, Bamberg M, Rodemann HP (1999) Radiation sensitivity of human squamous cell carcinoma cells in vitro is modulated by all-trans and 13-cis-retinoic acid in combination with interferon-alpha. Int J Radiat Oncol Biol Phys 45:991–998

    PubMed  CAS  Google Scholar 

  • Holsti LR, Mattson K, Niiranen A, Standertskiold-Nordenstam CG, Stenman S, Sovijarvi A, Cantell K (1987) Enhancement of radiation effects by alpha interferon in the treatment of small cell carcinoma of the lung. Int J Radiat Oncol Biol Phys 13:1161–1166

    PubMed  CAS  Google Scholar 

  • Hong JH, Chiang CS, Tsao CY, Lin PY, McBride WH, Wu CJ (1999) Rapid induction of cytokine gene expression in the lung after single and fractionated doses of radiation. Int J Radiat Biol 75:1421–1427

    PubMed  CAS  Google Scholar 

  • Huang FP, Platt N, Wykes M, Major JR, Powell TJ, Jenkins CD, MacPherson GG (2000) A discrete subpopulation of dendritic cells transports apoptotic intestinal epithelial cells to T cell areas of mesenteric lymph nodes. J Exp Med 191:435–444

    PubMed  CAS  Google Scholar 

  • Hughes AL, Yeager M (1997) Molecular evolution of the vertebrate immune system. Bioessays 19:777–786

    PubMed  CAS  Google Scholar 

  • Hunter N, Nakayama T, Ito H, Woo S, Milas L (1992) Combination of interleukin-2 and irradiation in therapy of murine tumors. Clin Exp Metastasis 10:431–436

    PubMed  Google Scholar 

  • Ikeguchi M, Ikeda M, Tatebe S, Maeta M, Kaibara N (1998) Clinical significance of dendritic cell infiltration in esophageal squamous cell carcinoma. Oncol Rep 5:1185–1189

    PubMed  CAS  Google Scholar 

  • Jee SH, Shen SC, Chiu HC, Tsai WL, Kuo ML (2001) Overexpression of interleukin-6 in human basal cell carcinoma cell lines increases anti-apoptotic activity and tumorigenic potency. Oncogene 20:198–208

    PubMed  CAS  Google Scholar 

  • Jett JR, Maksymiuk AW, Su JQ, Mailliard JA, Krook JE, Tschetter LK, Kardinal CG, Twito DI, Levitt R, Gerstner JB (1994) Phase III trial of recombinant interferon gamma in complete responders with small-cell lung cancer. J Clin Oncol 12:2321–2326

    PubMed  CAS  Google Scholar 

  • Johansson S, Landstrom M, Hellstrand K, Henriksson R (1998) The response of Dunning R3327 prostatic adeno-carcinoma to IL-2, histamine and radiation. Br J Cancer 77:1213–1219

    PubMed  CAS  Google Scholar 

  • Jonasch E, Haluska FG (2001) Interferon in oncological practice: review of interferon biology, clinical applications, and toxicities. Oncologist 6:34–55

    PubMed  CAS  Google Scholar 

  • Jurgenliemk-Schulz IM, Renes IB, Rutgers DH, Everse LA, Bernsen MR, Den Otter W, Battermann JJ (1997) Antitumor effects of local irradiation in combination with peritumoral administration of low doses of recombinant interleukin-2 (rIL-2). Radiat Oncol Invest 5:54–61

    CAS  Google Scholar 

  • Kang SM, Schneider DB, Lin Z, Hanahan D, Dichek DA, Stock PG, Baekkeskov S (1997) Fas ligand expression in islets of Langerhans does not confer immune privilege and instead targets them for rapid destruction. Nat Med 3: 738–743

    PubMed  CAS  Google Scholar 

  • Kawakita M, Rao GS, Ritchey JK, Ornstein DK, Hudson MA, Tartaglia J, Paoletti E, Humphrey PA, Harmon TJ, Ratliff TL (1997) Effect of canarypox virus (ALVAC)-mediated cytokine expression on murine prostate tumor growth. J Natl Cancer Inst 89:428–436

    PubMed  CAS  Google Scholar 

  • Kawase Y, Naito S, Ito M, Sekine I, Fujii H (1990) The effect of ionizing radiation on epidermal Langerhans cells — a quantitative analysis of autopsy cases with radiation therapy. J Radiat Res (Tokyo) 31:246–255

    CAS  Google Scholar 

  • Keilholz U, Goey SH, Punt CJ, Proebstle TM, Salzmann R, Scheibenbogen C, Schadendorf D, Lienard D, Enk A, Dummer R, Hantich B, Geueke AM, Eggermont AM (1997) Interferon alfa-2a and interleukin-2 with or without cisplatin in metastatic melanoma: a randomized trial of the European Organization for Research and Treatment of Cancer Melanoma Cooperative Group. J Clin Oncol 15: 2579–2588

    PubMed  CAS  Google Scholar 

  • Kimura M, Yoshida Y, Narita M, Takenaga K, Takenouchi T, Yamaguchi T, Saisho H, Sakiyama S, Tagawa M (1999) Acquired immunity in nude mice induced by expression of the IL-2 or IL-4 gene in human pancreatic carcinoma cells and anti-tumor effect generated by in vivo gene transfer using retrovirus. Int J Cancer 82:549–555

    PubMed  CAS  Google Scholar 

  • Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH (1996) Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol 14:7–17

    PubMed  CAS  Google Scholar 

  • Kodama T, Takeda K, Shimozato O, Hayakawa Y, Atsuta M, Kobayashi K, Ito M, Yagita H, Okumura K (1999) Perforin-dependent NK cell cytotoxicity is sufficient for anti-metastatic effect of IL-12. Eur J Immunol 29:1390–1396

    PubMed  CAS  Google Scholar 

  • Kontny HU, Lehrnbecher TM, Chanock SJ, Mackall CL (1998) Simultaneous expression of Fas and nonfunctional Fas ligand in Ewing’s sarcoma. Cancer Res 58:5842–5849

    PubMed  CAS  Google Scholar 

  • Kos FJ, Engleman EG (1996) Immune regulation: a critical link between NK cells and CTLs. Immunol Today 17: 174–176

    PubMed  CAS  Google Scholar 

  • Kovacs CJ, Gooya JM, Harrell JP, McGowan KM, Evans MJ (1991) Altered radioprotective properties of interleukin I alpha (IL-1) in non-hematologic tumor-bearing animals. Int J Radiat Oncol Biol Phys 20:307–310

    PubMed  CAS  Google Scholar 

  • Kurosawa S, Harada M, Matsuzaki G, Shinomiya Y, Terao H, Kobayashi N, Nomoto K (1995) Early-appearing tumour-infiltrating natural killer cells play a crucial role in the generation of anti-tumour T lymphocytes. Immunology 85:338–346

    PubMed  CAS  Google Scholar 

  • Kurzawa H, Wysocka M, Aruga E, Chang AE, Trinchieri G, Lee WM (1998) Recombinant interleukin 12 enhances cellular immune responses to vaccination only after a period of suppression. Cancer Res 58:491–499

    PubMed  CAS  Google Scholar 

  • Lange JR, Raubitschek AA, Pockaj BA, Spencer WF, Lotze MT, Topalian SL, Yang JC, Rosenberg SA (1992) A pilot study of the combination of interleukin-2-based immunotherapy and radiation therapy. J Immunother 12:265–271

    PubMed  CAS  Google Scholar 

  • Lappin MB, Campbell JD (2000) The Th1-Th2 classification of cellular immune responses: concepts, current thinking and applications in haematological malignancy. Blood Rev 14:228–239

    PubMed  CAS  Google Scholar 

  • Lee J, Moran JP, Fenton BM, Koch CJ, Frelinger JG, Keng PC, Lord EM (2000) Alteration of tumour response to radiation by interleukin-2 gene transfer. Br J Cancer 82:937-944 Lee S, Zheng M, Deshpande S, Eo SK, Hamilton TA, Rouse BT (2002) IL-12 suppresses the expression of ocular immuno-inflammatory lesions by effects on angiogenesis. J Leukoc Biol 71:469–476

    Google Scholar 

  • Legha SS, Ring S, Bedikian A, Plager C, Eton O, Buzaid AC, Papadopoulos N (1996) Treatment of metastatic melanoma with combined chemotherapy containing cisplatin, vinblastine and dacarbazine (CVD) and biotherapy using interleukin-2 and interferon-alpha. Ann Oncol 7:827–835

    PubMed  CAS  Google Scholar 

  • Lens MB, Dawes M (2002) Interferon alfa therapy for malignant melanoma: a systematic review of randomized controlled trials. J Clin Oncol 20:1818–1825

    PubMed  CAS  Google Scholar 

  • Leonard JP, Sherman ML, Fisher GL, Buchanan LJ, Larsen G, Atkins MB, Sosman JA, Dutcher JP, Vogelzang NJ, Ryan JL (1997) Effects of single-dose interleukin-12 exposure on interleukin-12-associated toxicity and interferon-gamma production. Blood 90:2541–2548

    PubMed  CAS  Google Scholar 

  • Levey DL, Srivastava PK (1995) T cells from late tumor-bearing mice express normal levels of p56lck, p59fyn, ZAP-70, and CD3 zeta despite suppressed cytolytic activity. J Exp Med 182:1029–1036

    PubMed  CAS  Google Scholar 

  • Levings MK, Sangregorio R, Roncarolo MG (2001) Human cd25(+)cd4(+) t regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function. J Exp Med 193:1295–1302

    PubMed  CAS  Google Scholar 

  • Lippman SM, Kavanagh JJ, Paredes-Espinoza M, Delgadillo-Madrueno F, Paredes-Casillas P, Hong WK, Massimini G, Holdener EE, Krakoff IH (1993) 13-cis-retinoic acid plus interferon-alpha 2a in locally advanced squamous cell carcinoma of the cervix. J Natl Cancer Inst 85:499–500

    PubMed  CAS  Google Scholar 

  • Lohr F, Hu K, Haroon Z, Samulski TV, Huang Q, Beaty J, Dewhirst MW, Li CY (2000a) Combination treatment of murine tumors by adenovirus-mediated local B7/IL12 immunotherapy and radiotherapy. Mol Ther 2:195–203

    PubMed  CAS  Google Scholar 

  • Lohr F, Hu K, Huang Q, Zhang L, Samulski TV, Dewhirst MW, Li CY (2000b) Enhancement of radiotherapy by hyperthermia-regulated gene therapy. Int J Radiat Oncol Biol Phys 48:1513–1518

    PubMed  CAS  Google Scholar 

  • Lohr F, Huang Q, Hu K, Dewhirst MW, Li CY (2001) Systemic vector leakage and transgene expression by intratumorally injected recombinant adenovirus vectors. Clin Cancer Res 7:3625–3628

    PubMed  CAS  Google Scholar 

  • Lucey DR (1999) Evolution of the type-1 (Th1)-type-2 (Th2) cytokine paradigm. Infect Dis Clin North Am 13:1–9

    PubMed  CAS  Google Scholar 

  • Maasilta P, Holsti LR, Halme M, Kivisaari L, Cantell K, Mattson K (1992) Natural alpha-interferon in combination with hyperfractionated radiotherapy in the treatment of non-small cell lung cancer. Int J Radiat Oncol Biol Phys 23:863–868

    PubMed  CAS  Google Scholar 

  • Mahjoubi R, Bachouchi M, Munck JN, Busson P, Gasmi J, Azli N, Brandely M, Trusz T, Cvitkovic E, Armand JP (1993) Phase II trial of recombinant interferon gamma in refractory undifferentiated carcinoma of the nasopharynx. Head Neck 15:115–118

    PubMed  CAS  Google Scholar 

  • Malone C, Schiltz PM, Nayak SK, Shea MW, Dillman RO (1999) Combination interferon-alpha2a and 13-cis-retinoic acid enhances radiosensitization of human malignant glioma cells in vitro. Clin Cancer Res 5:417–423

    PubMed  CAS  Google Scholar 

  • Mason KA, Tofilon PJ (1994) Unexpected radiation protection with 13-cis-retinoic acid plus interferon alpha-2a. Cancer Chemother Pharmacol 33:435–437

    PubMed  CAS  Google Scholar 

  • McDonald S, Chang AY, Rubin P, Wallenberg J, Kim IS, Sobel S, Smith J, Keng P, Muhs A (1993) Combined Betaseron R (recombinant human interferon beta) and radiation for inoperable non-small cell lung cancer. Int J Radiat Oncol Biol Phys 27:613–619

    PubMed  CAS  Google Scholar 

  • Medzhitov R, Janeway CA Jr (1997) Innate immunity: the virtues of a nonclonal system of recognition. Cell 91:295–298

    PubMed  CAS  Google Scholar 

  • Meeren AV, Gaugler MH, Mouthon MA, Squiban C, Gourmelon P(1999) Interleukin 4 promotes survival of lethally irradiated mice in the absence of hematopoietic efficacy. Radiat Res 152:629–636

    PubMed  Google Scholar 

  • Melero I, Duarte M, Ruiz J, Sangro B, Galofre J, Mazzolini G, Bustos M, Qian C, Prieto J (1999) Intratumoral injection of bone-marrow-derived dendritic cells engineered to produce interleukin-12 induces complete regression of established murine transplantable colon adenocarcinomas. Gene Ther 6:1779–1784

    PubMed  CAS  Google Scholar 

  • Meriggioli MN, Rowin J (2000) Chronic inflammatory demyelinating polyneuropathy after treatment with interferonalpha. Muscle Nerve 23:433–435

    PubMed  CAS  Google Scholar 

  • Mertens R, Granzen B, Lassay L, Gademann G, Hess CF, Heimann G (1997) Nasopharyngeal carcinoma in childhood and adolescence: concept and preliminary results of the cooperative GPOH study NPC-91. Gesellschaft für Padiatrische Onkologie und Hamatologie. Cancer 80:951–959

    PubMed  CAS  Google Scholar 

  • Miyamoto Y, Hosotani R, Doi R, Wada M, Ida J, Tsuji S, Kawaguchi M, Nakajima S, Kobayashi H, Masui T, Imamura M (2001) Interleukin-6 inhibits radiation-induced apoptosis in pancreatic cancer cells. Anticancer Res 21:2449–2456

    PubMed  CAS  Google Scholar 

  • Mizutani N, Fujikura Y, Wang YH, Tamechika M, Tokuda N, Sawada T, Fukumoto T (2002) Inflammatory and anti-inflammatory cytokines regulate the recovery from sublethal X irradiation in rat thymus. Radiat Res 157: 281–289

    PubMed  CAS  Google Scholar 

  • Mollman JE (1992) Neuromuscular toxicity of therapy. Curr Opin Oncol 4:540–546

    PubMed  CAS  Google Scholar 

  • Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765

    PubMed  CAS  Google Scholar 

  • Morel A, Fernandez N, de La Coste A, Haddada H, Viguier M, Polla BS, Antoine B, Kahn A (1998) Gamma-ray irradiation induces B7.1 costimulatory molecule neoexpression in various murine tumor cells. Cancer Immunol Immunother 46:277–282

    PubMed  CAS  Google Scholar 

  • Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136:2348–2357

    PubMed  CAS  Google Scholar 

  • Motzer RJ, Rakhit A, Schwartz LH, Olencki T, Malone TM, Sandstrom K, Nadeau R, Parmar H, Bukowski R (1998) Phase I trial of subcutaneous recombinant human interleukin-12 in patients with advanced renal cell carcinoma. Clin Cancer Res 4:1183–1191

    PubMed  CAS  Google Scholar 

  • Motzer RJ, Rakhit A, Thompson JA, Nemunaitis J, Murphy BA, Ellerhorst J, Schwartz LH, Berg WJ, Bukowski RM (2001) Randomized multicenter phase II trial of subcutaneous recombinant human interleukin-12 versus interferon-alpha 2a for patients with advanced renal cell carcinoma. J Interferon Cytokine Res 21:257–263

    PubMed  CAS  Google Scholar 

  • MRC/RCC (1999) Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomised controlled trial. Medical Research Council Renal Cancer Collaborators. Lancet 353:14–17

    Google Scholar 

  • Murad AM, Oliveira M, Saldanha TM (1994) Phase II trial of isotretinoin and interferon alpha-2a in the treatment of advanced recurrent cervical carcinoma. Int J Gynecol Cancer 4:414–418

    PubMed  Google Scholar 

  • Mushegian A, Medzhitov R (2001) Evolutionary perspective on innate immune recognition. J Cell Biol 155:705–710

    PubMed  CAS  Google Scholar 

  • Myers JN, Yasumura S, Suminami Y, Hirabayashi H, Lin W, Johnson JT, Lotze MT, Whiteside TL (1996) Growth stimulation of human head and neck squamous cell carcinoma cell lines by interleukin 4. Clin Cancer Res 2:127–135

    PubMed  CAS  Google Scholar 

  • Nanni P, Rossi I, De Giovanni C, Landuzzi L, Nicoletti G, Stoppacciaro A, Parenza M, Colombo MP, Lollini PL (1998) Interleukin 12 gene therapy of MHC-negative murine melanoma metastases. Cancer Res 58:1225–1230

    PubMed  CAS  Google Scholar 

  • Nasu Y, Bangma CH, Hull GW, Lee HM, Hu J, Wang J, McCurdy MA, Shimura S, Yang G, Timme TL, Thompson TC (1999) Adenovirus-mediated interleukin-12 gene therapy for prostate cancer: suppression of orthotopic tumor growth and pre-established lung metastases in an orthotopic model. Gene Ther 6:338–349

    PubMed  CAS  Google Scholar 

  • Nathan PD, Gore ME, Eisen TG (2002) Unexpected toxicity of combination thalidomide and interferon alpha-2a treatment in metastatic renal cell carcinoma. J Clin Oncol 20: 1429–1430

    PubMed  CAS  Google Scholar 

  • Neta R, Oppenheim JJ, Wang JM, Snapper CM, Moorman MA, Dubois CM (1994) Synergy of IL-1 and stem cell factor in radioprotection of mice is associated with IL-1 up-regulation of mRNA and protein expression for c-kit on bone marrow cells. J Immunol 153:1536–1543

    PubMed  CAS  Google Scholar 

  • Nishioka Y, Hirao M, Robbins PD, Lotze MT, Tahara H (1999) Induction of systemic and therapeutic antitumor immunity using intratumoral injection of dendritic cells genetically modified to express interleukin 12. Cancer Res 59: 4035–4041

    PubMed  CAS  Google Scholar 

  • Nishisaka N, Maini A, Kinoshita Y, Yasumoto R, Kishimoto T, Jones RF, Morse P, Hillman GG, Wang CY, Haas GP (1999) Immunotherapy for lung metastases of murine renal cell carcinoma: synergy between radiation and cytokine-producing tumor vaccines. J Immunother 22:308–314

    PubMed  CAS  Google Scholar 

  • Nishisaka N, Jones RF, Morse P, Kuratsukuri K, Romanowski R, Wang CY, Haas GP (2000) Inhibition of lung metastases of murine renal cell carcinoma by the combination of radiation and interferon-alpha-producing tumor cell vaccine. Cytokines Cell Mol Ther 6:199–206

    PubMed  CAS  Google Scholar 

  • North RJ, Bursuker I (1984) T cell-mediated suppression of the concomitant antitumor immune response as an example of transplantation tolerance. Transplant Proc 16:463–469

    PubMed  CAS  Google Scholar 

  • Nukui Y, Picozzi VJ, Traverso LW (2000) Interferon-based adjuvant chemoradiation therapy improves survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Am J Surg 179:367–371

    PubMed  CAS  Google Scholar 

  • Oboshi S, Shimosato Y, Itakura K, Umegaky S (1967) Radiation pathology for cancer II: the immunological significance of the infiltration of lymphocytes surrounding the tumor tissue during irradiation. Igakunoyumi 61:725–730

    Google Scholar 

  • Ochsenbein AF, Sierro S, Odermatt B, Pericin M, Karrer U, Hermans J, Hemmi S, Hengartner H, Zinkernagel RM (2001) Roles of tumour localization, second signals and cross priming in cytotoxic T-cell induction. Nature 411: 1058–1064

    PubMed  CAS  Google Scholar 

  • O’Connell J, Bennett MW, O’Sullivan GC, Collins JK, Shanahan F (1999) Fas counter-attack — the best form of tumor defense? Nat Med 5:267–268

    PubMed  Google Scholar 

  • Ogawa Y, Nishioka A, Kubonishi II, Inomata T, Yoshida S, Kataoka S (1998) Cytotoxicity of Fas ligand against lymphoma cells with radiation-induced Fas antigen. Int J Mol Med 2:435–436

    PubMed  CAS  Google Scholar 

  • Olkowski ZL (1999) Functional response of human natural killer (NK) cells to ionizing radiation. Int J Radiat Oncol Biol Phys 45:282–283

    Google Scholar 

  • O’Shea JJ, Ma A, Lipsky P (2002) Cytokines and autoimmunity. Nat Rev Immunol 2:37–45

    PubMed  Google Scholar 

  • Ostrand-Rosenberg S, Gunther V, Armstrong T, Pulaski B, Pipeling M, Clements V, Namouse-Smith N (1999) Immunologic targets for the gene therapy of cancer. In: Lattime EC, Gerson SL (eds) Gene therapy of cancer. Academic Press, New York

    Google Scholar 

  • Oyama T, Ran S, Ishida T, Nadaf S, Kerr L, Carbone DP, Gabrilovich DI (1998) Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoietic progenitor cells. J Immunol 160:1224–1232

    PubMed  CAS  Google Scholar 

  • Packer RJ, Prados M, Phillips P, Nicholson HS, Boyett JM, Goldwein J, Rorke LB, Needle MN, Sutton L, Zimmerman RA, Fitz CR, Vezina LG, Etcubanas E, Wallenberg JC, Reaman G, Wara W (1996) Treatment of children with newly diagnosed brain stem gliomas with intravenous recombinant beta-interferon and hyperfractionated radiation therapy: a children’s cancer group phase I/II study. Cancer 77:2150–2156

    PubMed  CAS  Google Scholar 

  • Pardoll DM, Topalian SL (1998) The role of CD4+ T cell responses in antitumor immunity. Curr Opin Immunol 10:588–594

    PubMed  CAS  Google Scholar 

  • Park TK, Lee JP, Kim SN, Choi SM, Kudelka AP, Kavanagh JJ (1998) Interferon-alpha 2a, 13-cis-retinoic acid and radiotherapy for locally advanced carcinoma of the cervix: a pilot study. Eur J Gynaecol Oncol 19:35–38

    PubMed  CAS  Google Scholar 

  • Patchen ML, MacVittie TJ, Williams JL, Schwartz GN, Souza LM (1991) Administration of interleukin-6 stimulates multilineage hematopoiesis and accelerates recovery from radiation-induced hematopoietic depression. Blood 77: 472–480

    PubMed  CAS  Google Scholar 

  • Pham-Nguyen KB, Yang W, Saxena R, Thung SN, Woo SL, Chen SH (1999) Role of NK and T cells in IL-12-induced anti-tumor response against hepatic colon carcinoma. Int J Cancer 81:813–819

    PubMed  CAS  Google Scholar 

  • Puisieux I, Odin L, Poujol D, Moingeon P, Tartaglia J, Cox W, Favrot M (1998) Canarypox virus-mediated interleukin 12 gene transfer into murine mammary adenocarcinoma induces tumor suppression and long-term antitumoral immunity. Hum Gene Ther 9:2481–2492

    PubMed  CAS  Google Scholar 

  • Radbruch A (2001) Immunsystem und Immunität (German). In: Zeidler H, Zacher J, Hiepe F (eds) Interdisziplinäre klinische Rheumatologie. Springer, Berlin Heidelberg New York, pp 4–25

    Google Scholar 

  • Raju U, Gumin GJ, Tofilon PJ (1999) NF kappa B activity and target gene expression in the rat brain after one and two exposures to ionizing radiation. Radiat Oncol Invest 7: 145–152

    CAS  Google Scholar 

  • Ratto GB, Zino P, Mirabelli S, Minuti P, Aquilina R, Fantino G, Spessa E, Ponte M, Bruzzi P, Melioli G (1996) A randomized trial of adoptive immunotherapy with tumor-infiltrating lymphocytes and interleukin-2 versus standard therapy in the postoperative treatment of resected nonsmall cell lung carcinoma. Cancer 78:244–251

    PubMed  CAS  Google Scholar 

  • Redman BG, Hillman GG, Flaherty L, Forman J, Dezso B, Haas GP (1998) Phase II trial of sequential radiation and interleukin 2 in the treatment of patients with metastatic renal cell carcinoma. Clin Cancer Res 4:283–286

    PubMed  CAS  Google Scholar 

  • Restifo N, Kawakami Y, Marincola F et al (1993) Molecular mechanisms used by tumors to escape immune recognition: immunotherapy and the cell biology of major histocompatibility complex I. J Immunother 14:182–190

    CAS  Google Scholar 

  • Roberts JL, Sharrow SO, Singer A (1990) Clonal deletion and clonal anergy in the thymus induced by cellular elements with different radiation sensitivities. J Exp Med 171: 935–940

    PubMed  CAS  Google Scholar 

  • Rosenberg SA, Yannelli JR, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, Seipp CA, Einhorn JH, White DE (1994) Treatment of patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and interleukin 2. J Natl Cancer Inst 86:1159–1166

    PubMed  CAS  Google Scholar 

  • Rosenberg SA, Yang JC, Schwartzentruber DJ, Hwu P, Marincola FM, Topalian SL, Seipp CA, Einhorn JH, White DE, Steinberg SM (1999) Prospective randomized trial of the treatment of patients with metastatic melanoma using chemotherapy with cisplatin, dacarbazine, and tamoxifen alone or in combination with interleukin-2 and interferon alfa-2b. J Clin Oncol 17:968–975

    PubMed  CAS  Google Scholar 

  • Roth C, Rochlitz C, Kourilsky P (1994) Immune response against tumors. Adv Immunol 57:281–351

    PubMed  CAS  Google Scholar 

  • Rübe C, Finke C, van Valen F, Schafer KL, Dockhorn-Dworniczak B, Willich N (1997) The demonstration of the radiation-induced production of tumor necrosis factor-alpha in Ewing’s sarcoma RM 82 in vitro and in vivo. Strahlenther Onkol 173:407–414

    PubMed  Google Scholar 

  • Sad S, Marcotte R, Mosmann TR (1995) Cytokine-induced differentiation of precursor mouse CD8+ T cells into cytotoxic CD8+ T cells secreting Th1 or Th2 cytokines. Immunity 2:271–279

    PubMed  CAS  Google Scholar 

  • Safwat A (2000) The immunobiology of low-dose total-body irradiation: more questions than answers. Radiat Res 153: 599–604

    PubMed  CAS  Google Scholar 

  • Santin A, Hermonat P, Ravaggi A, Chiriva-Internati M, Hiserodt J, Batchus R, Barclay D, Pecorelli S, Parham G (1998) The effects of irradiation on the expression of a tumor rejection antigen (heat shock protein gp96) in human cervical cancer. Int J Radiat Biol 73:699–704

    PubMed  CAS  Google Scholar 

  • Sareneva T, Julkunen I, Matikainen S (2000) IFN-alpha and IL-12 induce IL-18 receptor gene expression in human NK and T cells. J Immunol 165:1933–1938

    PubMed  CAS  Google Scholar 

  • Scanlan MJ, Chen YT, Williamson B, Gure AO, Stockert E, Gordan JD, Tureci O, Sahin U, Pfreundschuh M, Old LJ (1998) Characterization of human colon cancer antigens recognized by autologous antibodies. Int J Cancer 76: 652–658

    PubMed  CAS  Google Scholar 

  • Schiller JH, Pugh M, Kirkwood JM, Karp D, Larson M, Borden E (1996) Eastern cooperative group trial of interferon gamma in metastatic melanoma: an innovative study design. Clin Cancer Res 2:29–36

    PubMed  CAS  Google Scholar 

  • Schmidberger H, Rave-Frank M, Lehmann J, Schweinfurth S, Rehring E, Henckel K, Hess CF (1999) The combined effect of interferon beta and radiation on five human tumor cell lines and embryonal lung fibroblasts. Int J Radiat Oncol Biol Phys 43:405–412

    PubMed  CAS  Google Scholar 

  • Schrijvers D, Johnson J, Jiminez U, Gore M, Kosmidis P, Szpirglas H, Robbins K, Oliveira J, Lewensohn R, Schuller J, Riviere A, Arvay C, Langecker P, Jacob H, Cvitkovic E, Vokes E (1998) Phase III trial of modulation of cisplatin/ fluorouracil chemotherapy by interferon alfa-2b in patients with recurrent or metastatic head and neck cancer. Head and Neck Interferon Cooperative Study Group. J Clin Oncol 16:1054–1059

    PubMed  CAS  Google Scholar 

  • Schwartz RH (1990) A cell culture model for T lymphocyte clonal anergy. Science 248:1349–1356

    PubMed  CAS  Google Scholar 

  • Seetharam S, Staba MJ, Schumm LP, Schreiber K, Schreiber H, Kufe DW, Weichselbaum RR (1999) Enhanced eradication of local and distant tumors by genetically produced interleukin-12 and radiation. Int J Oncol 15:769–773

    PubMed  CAS  Google Scholar 

  • Seliger B, Harders C, Lohmann S, Momburg F, Urlinger S, Tampe R, Huber C (1998) Down-regulation of the MHC class I antigen-processing machinery after oncogenic transformation of murine fibroblasts. Eur J Immunol 28: 122–133

    PubMed  CAS  Google Scholar 

  • Shaw EG, Deming RL, Creagan ET, Nair S, Su JQ, Levitt R, Steen PD, Wiesenfeld M, Mailliard JA (1995) Pilot study of human recombinant interferon gamma and accelerated hyperfractionated thoracic radiation therapy in patients with unresectable stage IIIA/B nonsmall cell lung cancer. Int J Radiat Oncol Biol Phys 31:827–831

    PubMed  CAS  Google Scholar 

  • Shibata T, Akiyama N, Noda M, Sasai K, Hiraoka M (1998) Enhancement of gene expression under hypoxic conditions using fragments of the human vascular endothelial growth factor and the erythropoietin genes. Int J Radiat Oncol Biol Phys 42:913–916

    PubMed  CAS  Google Scholar 

  • Shin DM, Glisson BS, Khuri FR, Clifford JL, Clayman G, Benner SE, Forastiere AA, Ginsberg L, Liu D, Lee JJ, Myers J, Goepfert H, Lotan R, Hong WK, Lippman SM (2002) Phase II and biologic study of interferon alfa, retinoic acid, and cisplatin in advanced squamous skin cancer. J Clin Oncol 20:364–370

    PubMed  CAS  Google Scholar 

  • Shresta S, Pham CT, Thomas DA, Graubert TA, Ley TJ (1998) How do cytotoxic lymphocytes kill their targets? Curr Opin Immunol 10:581–587

    PubMed  CAS  Google Scholar 

  • Siefker-Radtke AO, Millikan RE, Tu SM, Moore DF Jr, Smith TL, Williams D, Logothetis CJ (2002) Phase III trial of fluorouracil, interferon alpha-2b, and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in metastatic or unresectable urothelial cancer. J Clin Oncol 20:1361–1367

    PubMed  CAS  Google Scholar 

  • Sornasse T, Larenas PV, Davis KA, de Vries JE, Yssel H (1996) Differentiation and stability of T helper 1 and 2 cells derived from naive human neonatal CD4+ T cells, analyzed at the single-cell level. J Exp Med 184:473–483

    PubMed  CAS  Google Scholar 

  • Srivastava P (2002) Roles of heat-shock proteins in innate and adaptive immunity. Nat Rev Immunol 2:185–194

    PubMed  CAS  Google Scholar 

  • Staveley-O’Carroll K, Sotomayor E, Montgomery J, Borrello I, Hwang L, Fein S, Pardoll D, Levitsky H (1998) Induction of antigen-specific T cell anergy: an early event in the course of tumor progression. Proc Natl Acad Sci U S A 95: 1178–1183

    PubMed  Google Scholar 

  • Steinbrink K, Jonuleit H, Muller G, Schuler G, Knop J, Enk AH (1999) Interleukin-10-treated human dendritic cells induce a melanoma-antigen-specific anergy in CD8(+) T cells resulting in a failure to lyse tumor cells. Blood 93: 1634–1642

    PubMed  CAS  Google Scholar 

  • Strasly M, Cavallo F, Geuna M, Mitola S, Colombo MP, Forni G, Bussolino F (2001) IL-12 inhibition of endothelial cell functions and angiogenesis depends on lymphocyte-endo-thelial cell cross-talk. J Immunol 166:3890–3899

    PubMed  CAS  Google Scholar 

  • Sun Y, Jurgovsky K, Moller P, Alijagic S, Dorbic T, Georgieva J, Wittig B, Schadendorf D (1998) Vaccination with IL-12 genemodified autologous melanoma cells: preclinical results and a first clinical phase I study. Gene Ther 5:481–490

    PubMed  CAS  Google Scholar 

  • Sun Y, Paschen A, Schadendorf D (1999) Cell-based vaccination against melanoma — background, preliminary results, and perspective. J Mol Med 77:593–608

    PubMed  CAS  Google Scholar 

  • Suto R, Srivastava PK (1995) A mechanism for the specific immunogenicity of heat shock protein-chaperoned peptides. Science 269:1585–1588

    PubMed  CAS  Google Scholar 

  • Takagi A, Imai A, Horibe S, Ohno T, Tamaya T (1998) Lack of evidence for expression of Fas ligand in Fas-bearing tumors. Oncol Rep 5:377–380

    PubMed  CAS  Google Scholar 

  • Takeuchi T, Ueki T, Sasaki Y, Kajiwara T, Li B, Moriyama N, Kawabe K (1997) Th2-like response and antitumor effect of anti-interleukin-4 mAb in mice bearing renal cell carcinoma. Cancer Immunol Immunother 43:375–381

    PubMed  CAS  Google Scholar 

  • Tamura Y, Peng P, Liu K, Daou M, Srivastava PK (1997) Immunotherapy of tumors with autologous tumor-derived heat shock protein preparations. Science 278:117–120

    PubMed  CAS  Google Scholar 

  • Taylor PA, Noelle RJ, Blazar BR (2001) CD4(+)CD25(+) immune regulatory cells are required for induction of tolerance to alloantigen via costimulatory blockade. J Exp Med 193:1311–1318

    PubMed  CAS  Google Scholar 

  • Teicher BA, Ara G, Buxton D, Leonard J, Schaub RG (1998) Optimal scheduling of interleukin-12 and fractionated radiation therapy in the murine Lewis lung carcinoma. Radiat Oncol Invest 6:71–80

    CAS  Google Scholar 

  • Thomas R, Stea B (2002) Radiation recall dermatitis from high-dose interferon alfa-2b. J Clin Oncol 20:355–357

    PubMed  Google Scholar 

  • Tisch M, Heimlich F, Daniel V, Opelz G, Maier H (1998) Cellular immune defect caused by postsurgical radiation therapy in patients with head and neck cancer. Otolaryngol Head Neck Surg 119:412–417

    PubMed  CAS  Google Scholar 

  • Todryk S, Melcher AA, Hardwick N, Linardakis E, Bateman A, Colombo MP, Stoppacciaro A, Vile RG (1999) Heat shock protein 70 induced during tumor cell killing induces Th1 cytokines and targets immature dendritic cell precursors to enhance antigen uptake. J Immunol 163:1398–1408

    PubMed  CAS  Google Scholar 

  • Toma S, Palumbo R, Vincenti M, Aitini E, Paganini G, Pronzato P, Grimaldi A, Rosso R (1994) Efficacy of recombinant alpha-interferon 2a and 13-cis-retinoic acid in the treatment of squamous cell carcinoma. Ann Oncol 5:463–465

    PubMed  CAS  Google Scholar 

  • Torrisi J, Berg C, Harter K, Lvovsky E, Yeung K, Woolley P, Bonnem E, Dritschilo A (1986) Phase I combined modality clinical trial of alpha-2-interferon and radiotherapy. Int J Radiat Oncol Biol Phys 12:1453–1456

    PubMed  CAS  Google Scholar 

  • Tourani JM, Pfister C, Berdah JF, Benhammouda A, Salze P, Monnier A, Paule B, Guillet P, Chretien Y, Brewer Y, Di Palma M, Untereiner M, Malaurie E, Tadrist Z, Pavlovitch JM, Hauteville D, Mejean A, Azagury M, Mayeur D, Lucas V, Krakowski I, Larregain-Fournier D, Abourachid H, Andrieu JM, Chastang C (1998) Outpatient treatment with subcutaneous interleukin-2 and interferon alfa administration in combination with fluorouracil in patients with metastatic renal cell carcinoma: results of a sequential nonrandomized phase II study. Subcutaneous Administration Proleukin Program Cooperative Group. J Clin Oncol 16:2505–2513

    PubMed  CAS  Google Scholar 

  • Townsend SE, Allison JP (1993) Tumor rejection after direct costimulation of CD8+ T cells by B7-transfected melanoma cells. Science 259:368–370

    PubMed  CAS  Google Scholar 

  • Treuner J, Niethammer D, Dannecker G, Hagmann R, Neef V, Hofschneider PH (1980) Successful treatment of nasopharyngeal carcinoma with interferon. Lancet 1:817–818

    PubMed  CAS  Google Scholar 

  • Van der Meeren A, Monti P, Lebaron-Jacobs L, Marquette C, Gourmelon P (2001) Characterization of the acute inflammatory response after irradiation in mice and its regulation by interleukin 4 (Il4). Radiat Res 155:858–865

    PubMed  Google Scholar 

  • Van Elsas A, Hurwitz AA, Allison JP (1999) Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J Exp Med 190:355–366

    Google Scholar 

  • Van Herpen CM, Jansen RL, Kruit WH, Hoekman K, Groenewegen G, Osanto S, De Mulder PH (2000) Immunoche-motherapy with interleukin-2, interferon-alpha and 5-fluorouracil for progressive metastatic renal cell carcinoma: a multicenter phase II study. Dutch Immunotherapy Working Party. Br J Cancer 82:772–776

    Google Scholar 

  • Veenstra KG, Jonak ZL, Trulli S, Gollob JA (2002) IL-12 induces monocyte IL-18 binding protein expression via IFN-gamma. J Immunol 168:2282–2287

    PubMed  CAS  Google Scholar 

  • Velders MP, Schreiber H, Kast WM (1998) Active immunization against cancer cells: impediments and advances. Semin Oncol 25:697–706

    PubMed  CAS  Google Scholar 

  • Verastegui-Aviles E, Mohar A, Mota A, Guadarrama A, De La Garza-Salazar J (1999) Combination of radiation therapy and interferon alpha-2b in patients with advanced cervical carcinoma: a pilot study. Int J Gynecol Cancer 9:401–405

    PubMed  Google Scholar 

  • Voest EE, Kenyon BM, O’Reilly MS, Truitt G, D’Amato RJ, Folkman J (1995) Inhibition of angiogenesis in vivo by interleukin 12. J Natl Cancer Inst 87:581–586

    PubMed  CAS  Google Scholar 

  • Vokes EE (1994) The promise of biochemical modulation in combined modality therapy. Semin Oncol 21:29–33

    PubMed  CAS  Google Scholar 

  • Waddick KG, Finnegan DM, Chelstrom LM, Uckun FM (1995) In vivo radiosensitizing effects of recombinant interleukin 6 on radiation resistant BCL-1 B-lineage leukemia cells in a murine syngeneic bone marrow transplant model system. Leuk Lymph 19:121–128

    CAS  Google Scholar 

  • Wang C, Quevedo ME, Lannutti BJ, Gordon KB, Guo D, Sun W, Paller AS (1999) In vivo gene therapy with interleukin-12 inhibits primary vascular tumor growth and induces apoptosis in a mouse model. J Invest Dermatol 112:775–781

    PubMed  CAS  Google Scholar 

  • Weiss GR, Liu PY, Alberts DS, Peng YM, Fisher E, Xu MJ, Scudder SA, Baker LH Jr, Moore DF, Lippman SM (1998) 13-cisretinoic acid or all-trans-retinoic acid plus interferon-alpha in recurrent cervical cancer: a Southwest Oncology Group phase II randomized trial. Gynecol Oncol 71:386–390

    PubMed  CAS  Google Scholar 

  • Windbichler GH, Hensler E, Widschwendter M, Posch A, Daxenbichler G, Fritsch E, Marth C (1996) Increased radiosensitivity by a combination of 9-cis-retinoic acid and interferon-y in breast cancer cells. Gynecol Oncol 61:387–394

    PubMed  CAS  Google Scholar 

  • Yamamoto T, Yoneda K, Ueta E, Doi S, Osaki T (2000) Enhanced apoptosis of squamous cell carcinoma cells by interleukin-2-activated cytotoxic lymphocytes combined with radiation and anticancer drugs. Eur J Cancer 36: 2007–2017

    PubMed  CAS  Google Scholar 

  • Yamaoka J, Kabashima K, Kawanishi M, Toda K, Miyachi Y (2002) Cytotoxicity of IFN-gamma and TNF-alpha for vascular endothelial cell is mediated by nitric oxide. Biochem Biophys Res Commun 291:780–786

    PubMed  CAS  Google Scholar 

  • Yamashita T, Mizukoshi T, Tomita K, Kobayashi H (1987) Antitumor immunity and tumor metastases as influenced by the radiation dosage in local radiotherapy. Gan No Rinsho 33:1205–1210

    PubMed  CAS  Google Scholar 

  • Younes E, Haas GP, Dezso B, Ali E, Maughan RL, Kukuruga MA, Montecillo E, Pontes JE, Hillman GG (1995a) Local tumor irradiation augments the response to IL-2 therapy in a murine renal adenocarcinoma. Cell Immunol 165: 243–251

    PubMed  CAS  Google Scholar 

  • Younes E, Haas GP, Dezso B, Ali E, Maughan RL, Montecillo E, Pontes JE, Hillman GG (1995b) Radiation-induced effects on murine kidney tumor cells: role in the interaction of local irradiation and immunotherapy. J Urol 153: 2029–2033

    PubMed  CAS  Google Scholar 

  • Yue FY, Geertsen R, Hemmi S, Burg G, Pavlovic J, Laine E, Dummer R (1999) IL-12 directly up-regulates the expression of HLA class I, HLA class II and ICAM-1 on human melanoma cells: a mechanism for its antitumor activity? Eur J Immunol 29:1762–1773

    PubMed  CAS  Google Scholar 

  • Zucali JR, Moreb J, Gibbons W, Alderman J, Suresh A, Zhang Y, Shelby B (1994) Radioprotection of hematopoietic stem cells by interleukin-1. Exp Hematol 22:130–135

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Klinische Radiologie, Sektion Strahlentherapie, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany

    F. Lohr MD & F. Wenz MD

  2. Department of Experimental Clinical Oncology, Aarhus University Hospital, Nørrebrogade 44, Building 5, 8000, Aarhus C, Denmark

    C. Herskind PhD

  3. Department of Pathology, University of California San Francisco School of Medicine, Parnassus Ave., San Francisco, CA, 94143, USA

    J. Lohr MD

  4. Department of Radiation Oncology, Duke University Medical Center, 201B MSRB, Box 3455, Durham, NC, 27710, USA

    C.-Y. Li PhD

Authors
  1. F. Lohr MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Wenz MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Herskind PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Lohr MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C.-Y. Li PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Straße 22, 81675, München, Germany

    Carsten Nieder MD

  2. Department of Experimental Radiation Oncology, UT MD Anderson Cancer Center, 1515 Holcombe Blvd., P.O. Box 66, Houston, TX, 77030, USA

    Luka Milas MD, PhD

  3. Department of Radiation Oncology, UT MD Anderson Cancer Center, 1515 Holcombe Blvd., P.O. Box 66, Houston, TX, 77030, USA

    K. Kian Ang MD, PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Lohr, F., Wenz, F., Herskind, C., Lohr, J., Li, CY. (2003). Enhancement of the Radiation Response with Interleukins and Interferons. In: Nieder, C., Milas, L., Ang, K.K. (eds) Modification of Radiation Response. Medical Radiology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55613-5_16

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-55613-5_16

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62670-8

  • Online ISBN: 978-3-642-55613-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation