Skip to main content
SpringerLink
Log in
Book cover

Cancer Immunology pp 73–86Cite as

Strategies to Target Tumor Immunosuppression

  • Chapter
  • First Online:

  • 3136 Accesses

Abstract

Several strategies, aimed at activating both innate and adaptive antitumor immunity, have been and are currently evaluated in clinical trials. In separate chapters of this book, these strategies are being reviewed and discussed.

An alternative option is to (also) target intratumoral immune escape mechanisms in order to enhance intratumoral antitumor responses. Based on their overall target aim, these strategies can be divided into two main categories: strategies that aim at enhancing intratumor homing of effector T cells and strategies to maintain the activity of these cells once they have reached the tumor site.

Currently used therapeutic strategies that attempt to increase homing of effector T cells to tumors are local tumor irradiation, blockade of endothelin receptors, and taxane-based chemotherapy. Strategies that aim to enhance antitumor activity of intratumor effector T cells, either by overcoming tumor-induced tolerance or by overriding the immunosuppressive mechanisms imposed during tumor development, are depletion or functional inhibition of immunosuppressive populations, blockade of negative regulatory factors, and blockade of tumor growth factor-beta (TGF-β)-induced signaling.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   139.99
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

Learn about institutional subscriptions

References

  1. Burnet FM. The concept of immunological surveillance. Prog Exp Tumor Res. 1970;13:1–27.

    CAS  PubMed  Google Scholar 

  2. Whiteside TL. Immune responses to malignancies. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S272–83.

    PubMed Central  PubMed  Google Scholar 

  3. Sahin U, Tureci O, Pfreundschuh M. Serological identification of human tumor antigens. Curr Opin Immunol. 1997;9(5):709–16.

    CAS  PubMed  Google Scholar 

  4. Lee PP, Yee C, Savage PA, Fong L, Brockstedt D, Weber JS, et al. Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nat Med. 1999;5(6):677–85.

    CAS  PubMed  Google Scholar 

  5. Rabinovich GA, Gabrilovich D, Sotomayor EM. Immunosuppressive strategies that are mediated by tumor cells. Annu Rev Immunol. 2007;25:267–96.

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Sadun RE, Sachsman SM, Chen X, Christenson KW, Morris WZ, Hu P, et al. Immune signatures of murine and human cancers reveal unique mechanisms of tumor escape and new targets for cancer immunotherapy. Clin Cancer Res. 2007;13(13):4016–25.

    CAS  PubMed  Google Scholar 

  7. Dunn GP, Koebel CM, Schreiber RD. Interferons, immunity and cancer immunoediting. Nat Rev Immunol. 2006;6(11):836–48.

    CAS  PubMed  Google Scholar 

  8. Schoenborn JR, Wilson CB. Regulation of interferon-gamma during innate and adaptive immune responses. Adv Immunol. 2007;96:41–101.

    CAS  PubMed  Google Scholar 

  9. Demeure CE, Yang LP, Byun DG, Ishihara H, Vezzio N, Delespesse G. Human naive CD4 T cells produce interleukin-4 at priming and acquire a Th2 phenotype upon repetitive stimulations in neutral conditions. Eur J Immunol. 1995;25(9):2722–5.

    CAS  PubMed  Google Scholar 

  10. Thomas DA, Massague J. TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell. 2005;8(5):369–80.

    CAS  PubMed  Google Scholar 

  11. Troy AJ, Summers KL, Davidson PJ, Atkinson CH, Hart DN. Minimal recruitment and activation of dendritic cells within renal cell carcinoma. Clin Cancer Res. 1998;4(3):585–93.

    CAS  PubMed  Google Scholar 

  12. Gabrilovich DI, Corak J, Ciernik IF, Kavanaugh D, Carbone DP. Decreased antigen presentation by dendritic cells in patients with breast cancer. Clin Cancer Res. 1997;3(3):483–90.

    CAS  PubMed  Google Scholar 

  13. Coventry BJ, Lee PL, Gibbs D, Hart DN. Dendritic cell density and activation status in human breast cancer – CD1a, CMRF-44, CMRF-56 and CD-83 expression. Br J Cancer. 2002;86(4):546–51.

    CAS  PubMed Central  PubMed  Google Scholar 

  14. Fiore F, Von Bergwelt-Baildon MS, Drebber U, Beyer M, Popov A, Manzke O, et al. Dendritic cells are significantly reduced in non-Hodgkin’s lymphoma and express less CCR7 and CD62L. Leuk Lymphoma. 2006;47(4):613–22.

    CAS  PubMed  Google Scholar 

  15. von Bergwelt-Baildon MS, Popov A, Saric T, Chemnitz J, Classen S, Stoffel MS, et al. CD25 and indoleamine 2,3-dioxygenase are up-regulated by prostaglandin E2 and expressed by tumor-associated dendritic cells in vivo: additional mechanisms of T-cell inhibition. Blood. 2006;108(1):228–37.

    Google Scholar 

  16. Khong HT, Wang QJ, Rosenberg SA. Identification of multiple antigens recognized by tumor-infiltrating lymphocytes from a single patient: tumor escape by antigen loss and loss of MHC expression. J Immunother. 2004;27(3):184–90.

    PubMed Central  PubMed  Google Scholar 

  17. Campoli M, Chang CC, Ferrone S. HLA class I antigen loss, tumor immune escape and immune selection. Vaccine. 2002;20 Suppl 4:A40–5.

    CAS  PubMed  Google Scholar 

  18. Lang S, Atarashi Y, Nishioka Y, Stanson J, Meidenbauer N, Whiteside TL. B7.1 on human carcinomas: costimulation of T cells and enhanced tumor-induced T-cell death. Cell Immunol. 2000;201(2):​132–43.

    CAS  PubMed  Google Scholar 

  19. Ochoa AC, Zea AH, Hernandez C, Rodriguez PC. Arginase, prostaglandins, and myeloid-derived suppressor cells in renal cell carcinoma. Clin Cancer Res. 2007;13(2 Pt 2):721s–6.

    CAS  PubMed  Google Scholar 

  20. Peranzoni E, Zilio S, Marigo I, Dolcetti L, Zanovello P, Mandruzzato S, et al. Myeloid-derived suppressor cell heterogeneity and subset definition. Curr Opin Immunol. 2010;22(2):238–44.

    CAS  PubMed  Google Scholar 

  21. Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9(3):162–74.

    CAS  PubMed Central  PubMed  Google Scholar 

  22. Almand B, Clark JI, Nikitina E, van Beynen J, English NR, Knight SC, et al. Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol. 2001;166(1):678–89.

    CAS  PubMed  Google Scholar 

  23. Gabrilovich DI, Bronte V, Chen SH, Colombo MP, Ochoa A, Ostrand-Rosenberg S, et al. The terminology issue for myeloid-derived suppressor cells. Cancer Res. 2007;67(1):425–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  24. Bronte V, Zanovello P. Regulation of immune responses by L-arginine metabolism. Nat Rev Immunol. 2005;5(8):641–54.

    CAS  PubMed  Google Scholar 

  25. Rodriguez PC, Ochoa AC. Arginine regulation by myeloid derived suppressor cells and tolerance in cancer: mechanisms and therapeutic perspectives. Immunol Rev. 2008;222:180–91.

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Kusmartsev S, Nefedova Y, Yoder D, Gabrilovich DI. Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J Immunol. 2004;172(2):989–99.

    CAS  PubMed  Google Scholar 

  27. Goni O, Alcaide P, Fresno M. Immunosuppression during acute Trypanosoma cruzi infection: involvement of Ly6G (Gr1(+))CD11b(+) immature myeloid suppressor cells. Int Immunol. 2002;14(10):1125–34.

    CAS  PubMed  Google Scholar 

  28. Harari O, Liao JK. Inhibition of MHC II gene transcription by nitric oxide and antioxidants. Curr Pharm Des. 2004;10(8):893–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Bingisser RM, Tilbrook PA, Holt PG, Kees UR. Macrophage-derived nitric oxide regulates T cell activation via reversible disruption of the Jak3/STAT5 signaling pathway. J Immunol. 1998;160(12):5729–34.

    CAS  PubMed  Google Scholar 

  30. Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004;10(9):942–9.

    CAS  PubMed  Google Scholar 

  31. Zou W. Regulatory T, cells, tumour immunity and immunotherapy. Nat Rev Immunol. 2006;6(4):295–307.

    CAS  PubMed  Google Scholar 

  32. Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, Rudensky AY. Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity. 2005;22(3):329–41.

    CAS  PubMed  Google Scholar 

  33. Sasada T, Kimura M, Yoshida Y, Kanai M, Takabayashi A. CD4 + CD25+ regulatory T cells in patients with gastrointestinal malignancies: possible involvement of regulatory T cells in disease progression. Cancer. 2003;98(5):1089–99.

    PubMed  Google Scholar 

  34. Strauss L, Bergmann C, Szczepanski M, Gooding W, Johnson JT, Whiteside TL. A unique subset of CD4 + CD25highFoxp3+ T cells secreting interleukin-10 and transforming growth factor-beta1 mediates suppression in the tumor microenvironment. Clin Cancer Res. 2007;13(15 Pt 1):4345–54.

    CAS  PubMed  Google Scholar 

  35. Gordon S. Alternative activation of macrophages. Nat Rev Immunol. 2003;3(1):23–35.

    CAS  PubMed  Google Scholar 

  36. Lucas T, Abraham D, Aharinejad S. Modulation of tumor associated macrophages in solid tumors. Front Biosci. 2008;13:5580–8.

    CAS  PubMed  Google Scholar 

  37. Murdoch C, Giannoudis A, Lewis CE. Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues. Blood. 2004;104(8):2224–34.

    CAS  PubMed  Google Scholar 

  38. Bergers G, Coussens LM. Extrinsic regulators of epithelial tumor progression: metalloproteinases. Curr Opin Genet Dev. 2000;10(1):120–7.

    CAS  PubMed  Google Scholar 

  39. Lepique AP, Daghastanli KR, Cuccovia IM, Villa LL. HPV16 tumor associated macrophages suppress antitumor T cell responses. Clin Cancer Res. 2009;15(13):4391–400.

    CAS  PubMed  Google Scholar 

  40. Bolpetti A, Silva JS, Villa LL, Lepique AP. Interleukin-10 production by tumor infiltrating macrophages plays a role in Human Papillomavirus 16 tumor growth. BMC Immunol. 2010;11:27.

    PubMed Central  PubMed  Google Scholar 

  41. Donkor MK, Sarkar A, Li MO. Tgf-beta1 produced by activated CD4(+) T cells antagonizes T cell surveillance of tumor development. Oncoimmunology. 2012;1(2):162–71.

    PubMed Central  PubMed  Google Scholar 

  42. Lutz MB, Suri RM, Niimi M, Ogilvie AL, Kukutsch NA, Rossner S, et al. Immature dendritic cells generated with low doses of GM-CSF in the absence of IL-4 are maturation resistant and prolong allograft survival in vivo. Eur J Immunol. 2000;30(7):1813–22.

    CAS  PubMed  Google Scholar 

  43. Dolcetti L, Peranzoni E, Ugel S, Marigo I, Fernandez Gomez A, Mesa C, et al. Hierarchy of immunosuppressive strength among myeloid-derived suppressor cell subsets is determined by GM-CSF. Eur J Immunol. 2010;40(1):22–35.

    CAS  PubMed  Google Scholar 

  44. Morales JK, Kmieciak M, Knutson KL, Bear HD, Manjili MH. GM-CSF is one of the main breast tumor-derived soluble factors involved in the differentiation of CD11b-Gr1- bone marrow progenitor cells into myeloid-derived suppressor cells. Breast Cancer Res Treat. 2010;123(1):39–49.

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Munn DH. Indoleamine 2,3-dioxygenase, tumor-induced tolerance and counter-regulation. Curr Opin Immunol. 2006;18(2):220–5.

    CAS  PubMed  Google Scholar 

  46. Obermajer N, Muthuswamy R, Lesnock J, Edwards RP, Kalinski P. Positive feedback between PGE2 and COX2 redirects the differentiation of human dendritic cells toward stable myeloid-derived suppressor cells. Blood. 2011;118(20):5498–505.

    CAS  PubMed Central  PubMed  Google Scholar 

  47. Gazzaniga S, Bravo AI, Guglielmotti A, van Rooijen N, Maschi F, Vecchi A, et al. Targeting tumor-associated macrophages and inhibition of MCP-1 reduce angiogenesis and tumor growth in a human melanoma xenograft. J Invest Dermatol. 2007;127(8):2031–41.

    CAS  PubMed  Google Scholar 

  48. Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, Sharpe AH, et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 2006;439(7077):682–7.

    CAS  PubMed  Google Scholar 

  49. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–34.

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Curiel TJ, Wei S, Dong H, Alvarez X, Cheng P, Mottram P, et al. Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med. 2003;9(5):562–7.

    CAS  PubMed  Google Scholar 

  51. Parry RV, Chemnitz JM, Frauwirth KA, Lanfranco AR, Braunstein I, Kobayashi SV, et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol Cell Biol. 2005;25(21):9543–53.

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Huang CT, Workman CJ, Flies D, Pan X, Marson AL, Zhou G, et al. Role of LAG-3 in regulatory T cells. Immunity. 2004;21(4):503–13.

    CAS  PubMed  Google Scholar 

  53. Egen JG, Kuhns MS, Allison JP. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat Immunol. 2002;3(7):611–8.

    CAS  PubMed  Google Scholar 

  54. Levin ER. Endothelins. N Engl J Med. 1995;333(6):356–63.

    CAS  PubMed  Google Scholar 

  55. Abdel-Wahab Z, Dar MM, Hester D, Vervaert C, Gangavalli R, Barber J, et al. Effect of irradiation on cytokine production, MHC antigen expression, and vaccine potential of interleukin-2 and interferon-gamma gene-modified melanoma cells. Cell Immunol. 1996;171(2):246–54.

    CAS  PubMed  Google Scholar 

  56. Buckanovich RJ, Facciabene A, Kim S, Benencia F, Sasaroli D, Balint K, et al. Endothelin B receptor mediates the endothelial barrier to T cell homing to tumors and disables immune therapy. Nat Med. 2008;14(1):28–36.

    CAS  PubMed  Google Scholar 

  57. Gohji K, Kitazawa S, Tamada H, Katsuoka Y, Nakajima M. Expression of endothelin receptor a associated with prostate cancer progression. J Urol. 2001;165(3):1033–6.

    CAS  PubMed  Google Scholar 

  58. Venuti A, Salani D, Manni V, Poggiali F, Bagnato A. Expression of endothelin 1 and endothelin A receptor in HPV-associated cervical carcinoma: new potential targets for anticancer therapy. FASEB J. 2000;14(14):2277–83.

    CAS  PubMed  Google Scholar 

  59. Eltze E, Bertolin M, Korsching E, Wulfing P, Maggino T, Lelle R. Expression and prognostic relevance of endothelin-B receptor in vulvar cancer. Oncol Rep. 2007;18(2):305–11.

    CAS  PubMed  Google Scholar 

  60. Ganswindt U, Paulsen F, Corvin S, Eichhorn K, Glocker S, Hundt I, et al. Intensity modulated radiotherapy for high risk prostate cancer based on sentinel node SPECT imaging for target volume definition. BMC Cancer. 2005;5:91.

    PubMed Central  PubMed  Google Scholar 

  61. Kotera Y, Shimizu K, Mule JJ. Comparative analysis of necrotic and apoptotic tumor cells as a source of antigen(s) in dendritic cell-based immunization. Cancer Res. 2001;61(22):8105–9.

    CAS  PubMed  Google Scholar 

  62. Demaria S, Bhardwaj N, McBride WH, Formenti SC. Combining radiotherapy and immunotherapy: a revived partnership. Int J Radiat Oncol Biol Phys. 2005;63(3):655–66.

    PubMed Central  PubMed  Google Scholar 

  63. Friedman EJ. Immune modulation by ionizing radiation and its implications for cancer immunotherapy. Curr Pharm Des. 2002;8(19):1765–80.

    CAS  PubMed  Google Scholar 

  64. Ganss R, Ryschich E, Klar E, Arnold B, Hammerling GJ. Combination of T-cell therapy and trigger of inflammation induces remodeling of the vasculature and tumor eradication. Cancer Res. 2002;62(5):1462–70.

    CAS  PubMed  Google Scholar 

  65. Lugade AA, Moran JP, Gerber SA, Rose RC, Frelinger JG, Lord EM. Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J Immunol. 2005;174(12):7516–23.

    CAS  PubMed  Google Scholar 

  66. Nesslinger NJ, Sahota RA, Stone B, Johnson K, Chima N, King C, et al. Standard treatments induce antigen-specific immune responses in prostate cancer. Clin Cancer Res. 2007;13(5):1493–502.

    CAS  PubMed  Google Scholar 

  67. Schaue D, Ratikan JA, Iwamoto KS, McBride WH. Maximizing tumor immunity with fractionated radiation. Int J Radiat Oncol Biol Phys. 2012;83(4):1306–10.

    CAS  PubMed Central  PubMed  Google Scholar 

  68. Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S, et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012;366(10):925–31.

    CAS  PubMed Central  PubMed  Google Scholar 

  69. Khan MA, Partin AW. Endothelin-a receptor antagonists and advanced prostate cancer. Rev Urol. 2004;6(1):47–8.

    PubMed Central  PubMed  Google Scholar 

  70. Akhavan A, McHugh KH, Guruli G, Bies RR, Zamboni WC, Strychor SA, et al. Endothelin receptor A blockade enhances taxane effects in prostate cancer. Neoplasia. 2006;8(9):725–32.

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Bagnato A, Rosano L, Spinella F, Di Castro V, Tecce R, Natali PG. Endothelin B receptor blockade inhibits dynamics of cell interactions and communications in melanoma cell progression. Cancer Res. 2004;64(4):1436–43.

    CAS  PubMed  Google Scholar 

  72. Kandalaft LE, Facciabene A, Buckanovich RJ, Coukos G. Endothelin B receptor, a new target in cancer immune therapy. Clin Cancer Res. 2009;15(14):4521–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Haldar S, Jena N, Croce CM. Inactivation of Bcl-2 by phosphorylation. Proc Natl Acad Sci U S A. 1995;92(10):4507–11.

    CAS  PubMed Central  PubMed  Google Scholar 

  74. Dirkx AE, oude Egbrink MG, Castermans K, van der Schaft DW, Thijssen VL, Dings RP, et al. Anti-angiogenesis therapy can overcome endothelial cell anergy and promote leukocyte-endothelium interactions and infiltration in tumors. FASEB J. 2006;20(6):621–30.

    CAS  PubMed  Google Scholar 

  75. Loffler A, Kufer P, Lutterbuse R, Zettl F, Daniel PT, Schwenkenbecher JM, et al. A recombinant bispecific single-chain antibody, CD19 x CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes. Blood. 2000;95(6):2098–103.

    CAS  PubMed  Google Scholar 

  76. Marme A, Strauss G, Bastert G, Grischke EM, Moldenhauer G. Intraperitoneal bispecific antibody (HEA125xOKT3) therapy inhibits malignant ascites production in advanced ovarian carcinoma. Int J Cancer. 2002;101(2):183–9.

    CAS  PubMed  Google Scholar 

  77. Nagaraj S, Youn JI, Weber H, Iclozan C, Lu L, Cotter MJ, et al. Anti-inflammatory triterpenoid blocks immune suppressive function of MDSCs and improves immune response in cancer. Clin Cancer Res. 2010;16(6):1812–23.

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Ko JS, Zea AH, Rini BI, Ireland JL, Elson P, Cohen P, et al. Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res. 2009;15(6):2148–57.

    CAS  PubMed  Google Scholar 

  79. Ko JS, Rayman P, Ireland J, Swaidani S, Li G, Bunting KD, et al. Direct and differential suppression of myeloid-derived suppressor cell subsets by sunitinib is compartmentally constrained. Cancer Res. 2010;70(9):3526–36.

    CAS  PubMed Central  PubMed  Google Scholar 

  80. Vincent J, Mignot G, Chalmin F, Ladoire S, Bruchard M, Chevriaux A, et al. 5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity. Cancer Res. 2010;70(8):3052–61.

    CAS  PubMed  Google Scholar 

  81. Shimizu J, Yamazaki S, Sakaguchi S. Induction of tumor immunity by removing CD25 + CD4+ T cells: a common basis between tumor immunity and autoimmunity. J Immunol. 1999;163(10):5211–8.

    CAS  PubMed  Google Scholar 

  82. Biswas S, Eisen T. Immunotherapeutic strategies in kidney cancer–when TKIs are not enough. Nat Rev Clin Oncol. 2009;6(8):478–87.

    CAS  PubMed  Google Scholar 

  83. Finke JH, Rini B, Ireland J, Rayman P, Richmond A, Golshayan A, et al. Sunitinib reverses type-1 immune suppression and decreases T-regulatory cells in renal cell carcinoma patients. Clin Cancer Res. 2008;14(20):6674–82.

    CAS  PubMed  Google Scholar 

  84. Mahnke K, Schonfeld K, Fondel S, Ring S, Karakhanova S, Wiedemeyer K, et al. Depletion of CD4 + CD25+ human regulatory T cells in vivo: kinetics of Treg depletion and alterations in immune functions in vivo and in vitro. Int J Cancer. 2007;120(12):2723–33.

    CAS  PubMed  Google Scholar 

  85. Rech AJ, Vonderheide RH. Clinical use of anti-CD25 antibody daclizumab to enhance immune responses to tumor antigen vaccination by targeting regulatory T cells. Ann N Y Acad Sci. 2009;1174:99–106.

    CAS  PubMed  Google Scholar 

  86. Klages K, Mayer CT, Lahl K, Loddenkemper C, Teng MW, Ngiow SF, et al. Selective depletion of Foxp3+ regulatory T cells improves effective therapeutic vaccination against established melanoma. Cancer Res. 2010;70(20):7788–99.

    CAS  PubMed  Google Scholar 

  87. Walczak M, Regts J, van Oosterhout AJ, Boon L, Wilschut J, Nijman HW, et al. Role of regulatory T-cells in immunization strategies involving a recombinant alphavirus vector system. Antivir Ther. 2011;16(2):207–18.

    PubMed  Google Scholar 

  88. Kaminetzky D, Hymes KB. Denileukin diftitox for the treatment of cutaneous T-cell lymphoma. Biologics. 2008;2(4):717–24.

    CAS  PubMed Central  PubMed  Google Scholar 

  89. Dannull J, Su Z, Rizzieri D, Yang BK, Coleman D, Yancey D, et al. Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest. 2005;115(12):3623–33.

    CAS  PubMed Central  PubMed  Google Scholar 

  90. Waldmann TA. Daclizumab (anti-Tac, Zenapax) in the treatment of leukemia/lymphoma. Oncogene. 2007;26(25):3699–703.

    CAS  PubMed  Google Scholar 

  91. Waldmann TA. Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey. J Clin Immunol. 2007;27(1):1–18.

    CAS  PubMed  Google Scholar 

  92. Liu DV, Maier LM, Hafler DA, Wittrup KD. Engineered interleukin-2 antagonists for the inhibition of regulatory T cells. J Immunother. 2009;32(9):887–94.

    CAS  PubMed Central  PubMed  Google Scholar 

  93. Ghiringhelli F, Menard C, Puig PE, Ladoire S, Roux S, Martin F, et al. Metronomic cyclophosphamide regimen selectively depletes CD4 + CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother. 2007;56(5):641–8.

    CAS  PubMed  Google Scholar 

  94. Sasahira T, Sasaki T, Kuniyasu H. Interleukin-15 and transforming growth factor alpha are associated with depletion of tumor-associated macrophages in colon cancer. J Exp Clin Cancer Res. 2005;24(1):69–74.

    CAS  PubMed  Google Scholar 

  95. Klebanoff CA, Finkelstein SE, Surman DR, Lichtman MK, Gattinoni L, Theoret MR, et al. IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells. Proc Natl Acad Sci U S A. 2004;101(7):1969–74.

    CAS  PubMed Central  PubMed  Google Scholar 

  96. Teague RM, Sather BD, Sacks JA, Huang MZ, Dossett ML, Morimoto J, et al. Interleukin-15 rescues tolerant CD8+ T cells for use in adoptive immunotherapy of established tumors. Nat Med. 2006;12(3):335–41.

    CAS  PubMed  Google Scholar 

  97. Lewen S, Zhou H, Hu HD, Cheng T, Markowitz D, Reisfeld RA, et al. A Legumain-based minigene vaccine targets the tumor stroma and suppresses breast cancer growth and angiogenesis. Cancer Immunol Immunother. 2008;57(4):507–15.

    CAS  PubMed  Google Scholar 

  98. Zeisberger SM, Odermatt B, Marty C, Zehnder-Fjallman AH, Ballmer-Hofer K, Schwendener RA. Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach. Br J Cancer. 2006;95(3):272–81.

    CAS  PubMed Central  PubMed  Google Scholar 

  99. Giraudo E, Inoue M, Hanahan D. An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis. J Clin Invest. 2004;114(5):623–33.

    CAS  PubMed Central  PubMed  Google Scholar 

  100. Caserta S, Alessi P, Basso V, Mondino A. IL-7 is superior to IL-2 for ex vivo expansion of tumour-specific CD4(+) T cells. Eur J Immunol. 2010;40(2):470–9.

    CAS  PubMed  Google Scholar 

  101. Rosenberg SA, Sportes C, Ahmadzadeh M, Fry TJ, Ngo LT, Schwarz SL, et al. IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells. J Immunother. 2006;29(3):313–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  102. Colombo MP, Trinchieri G. Interleukin-12 in anti-tumor immunity and immunotherapy. Cytokine Growth Factor Rev. 2002;13(2):155–68.

    CAS  PubMed  Google Scholar 

  103. Adams GP, Weiner LM. Monoclonal antibody therapy of cancer. Nat Biotechnol. 2005;23(9):1147–57.

    CAS  PubMed  Google Scholar 

  104. Kalergis AM, Ravetch JV. Inducing tumor immunity through the selective engagement of activating Fcgamma receptors on dendritic cells. J Exp Med. 2002;195(12):1653–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  105. Engelhardt JJ, Sullivan TJ, Allison JP. CTLA-4 overexpression inhibits T cell responses through a CD28-B7-dependent mechanism. J Immunol. 2006;177(2):1052–61.

    CAS  PubMed  Google Scholar 

  106. Sarnaik AA, Weber JS. Recent advances using anti-CTLA-4 for the treatment of melanoma. Cancer J. 2009;15(3):169–73.

    CAS  PubMed  Google Scholar 

  107. Riley JL. PD-1 signaling in primary T cells. Immunol Rev. 2009;229(1):114–25.

    CAS  PubMed Central  PubMed  Google Scholar 

  108. Iwai Y, Terawaki S, Honjo T. PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells. Int Immunol. 2005;17(2):133–44.

    CAS  PubMed  Google Scholar 

  109. Pilon-Thomas S, Mackay A, Vohra N, Mule JJ. Blockade of programmed death ligand 1 enhances the therapeutic efficacy of combination immunotherapy against melanoma. J Immunol. 2010;184(7):3442–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  110. Grosso JF, Kelleher CC, Harris TJ, Maris CH, Hipkiss EL, De Marzo A, et al. LAG-3 regulates CD8+ T cell accumulation and effector function in murine self- and tumor-tolerance systems. J Clin Invest. 2007;117(11):3383–92.

    CAS  PubMed Central  PubMed  Google Scholar 

  111. Grosso JF, Goldberg MV, Getnet D, Bruno TC, Yen HR, Pyle KJ, et al. Functionally distinct LAG-3 and PD-1 subsets on activated and chronically stimulated CD8 T cells. J Immunol. 2009;182(11):6659–69.

    CAS  PubMed Central  PubMed  Google Scholar 

  112. Zhang Q, Yang X, Pins M, Javonovic B, Kuzel T, Kim SJ, et al. Adoptive transfer of tumor-reactive transforming growth factor-beta-insensitive CD8+ T cells: eradication of autologous mouse prostate cancer. Cancer Res. 2005;65(5):1761–9.

    CAS  PubMed  Google Scholar 

  113. Terabe M, Ambrosino E, Takaku S, O’Konek JJ, Venzon D, Lonning S, et al. Synergistic enhancement of CD8+ T cell-mediated tumor vaccine efficacy by an anti-transforming growth factor-beta monoclonal antibody. Clin Cancer Res. 2009;15(21):6560–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  114. Wang FL, Qin WJ, Wen WH, Tian F, Song B, Zhang Q, et al. TGF-beta insensitive dendritic cells: an efficient vaccine for murine prostate cancer. Cancer Immunol Immunother. 2007;56(11):1785–93.

    CAS  PubMed  Google Scholar 

  115. Khalil M, Vonderheide RH. Anti-CD40 agonist antibodies: preclinical and clinical experience. Updat Cancer Ther. 2007;2(2):61–5.

    Google Scholar 

  116. Vonderheide RH. Prospect of targeting the CD40 pathway for cancer therapy. Clin Cancer Res. 2007;13(4):1083–8.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen, University of Groningen, 30.001, Groningen, 9700 RB, The Netherlands

    Oana Draghiciu MSc, PhD & Toos Daemen PhD

  2. Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, 30.001, Groningen, 9700 RB, The Netherlands

    Hans W. Nijman PhD

  3. Department of Medical Microbiology, Section of Tumor Virology and Cancer Immunotherapy, University Medical Center Groningen, University of Groningen, Groningen, 9700 RB, The Netherlands

    Toos Daemen PhD

Authors
  1. Oana Draghiciu MSc, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hans W. Nijman PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Toos Daemen PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Toos Daemen PhD .

Editor information

Editors and Affiliations

  1. Research Center for Immunodeficiencies, Children’s Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran

    Nima Rezaei

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Draghiciu, O., Nijman, H.W., Daemen, T. (2015). Strategies to Target Tumor Immunosuppression. In: Rezaei, N. (eds) Cancer Immunology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-44946-2_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-44946-2_5

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-44945-5

  • Online ISBN: 978-3-662-44946-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation