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Immunogenicity of tumour associated antigens

  • Chapter
Cancer Immunology

Part of the book series: Immunology and Medicine Series ((IMME,volume 30))

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Abstract

The continuing discovery of new tumor-associated/specific antigens, many of which are discussed in succeeding chapters in the first half of this book, document that at least some (most?) types of cancer are antigenic. Within the past five years, the number of molecular and cellular immunological techniques for identifying tumour-associated antigens has increased to such extent that over 100 distinct genes have now been associated with the transformation process. These antigens have been classified into several sub-groups and include for example proteins that are either mutated [1, 2], over-expressed [3, 4], associated with embryo-genesis [5] or differentiation [6]. They also include novel products that arise due to genetic translocations such as BCR-Abl [7, 8]. Melanoma is particularly interesting from an immunological perspective because it contains a wide spectrum of tissue-restricted proteins (e.g., MART-1, MAGE, gp100, tyrosinase, TRP-1, and TRP-2) that serve as targets of effector T cells in vitro [9–13]; see also Chapters 3 and 4. However, in vivo, adequate spontaneous activation of tumor-specific lymphocytes either does not occur or it results in inefficient tumor protection. Why tumors that are clearly antigenic are so clearly nonimmunogenic has puzzled investigators for years. Aspects of this paradox will be considered in this introductory chapter, including tolerance, antigen processing and the role of dendritic cells, and the nature of the response induced in terms of the balance between cellular immunity (Thl type response) and antibody responses (Th2 type response).

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References

  1. Hainaut P and Hollstein M, p53 and human cancer: The first ten thousand mutations. Adv Cancer Res, 2000; 77: 81–137.

    Article  PubMed  CAS  Google Scholar 

  2. Zweemer RP, Shaw PA, Verheijen RMH, Ryan A, Berchuck A, Ponder BAJ, Risch H, McLaughlin JR, Narod SA, Menko FH, Kenemans P, and Jacobs IJ, Accumulation of p53 protein is frequent in ovarian cancers associated with BRCA1 and BRCA2 germüne mutations. J Clin Pathol, 1999; 52: 372–375.

    Article  PubMed  CAS  Google Scholar 

  3. Duffour MT, Chaux P, Lurquin C, Comelis G, Boon T, and vanderBruggen P, A MAGE-A4 peptide presented by HLA-A2 is recognized by cytolytic T lymphocytes. Eur J Immunol, 1999; 29: 3329–3337.

    Article  PubMed  CAS  Google Scholar 

  4. Ruschenburg I, Kubitz A, Schlott T, Korabiowska M, and Droese M, MAGE-1, GAGE-1/-2 gene expression in FNAB of classic variant of papillary thyroid carcinoma and papillary hyperplasia in nodular goiter. lnt J Mol Med, 1999; 4: 445–448.

    CAS  Google Scholar 

  5. Fuller GN, Rhee CH, Hess KR, Caskey LS, Wang RP, Bruner JM, Yung WKA, and Zhang W, Reactivation of insulin-like growth factor binding protein 2 expression in glioblastoma multiforme: A revelation by parallel gene expression profiling Cancer Res, 1999; 59: 4228–4232.

    CAS  Google Scholar 

  6. Kittlesen DJ, Thompson LW, Gulden PH, Skipper JCA, Colella TA, Shabanowitz JA, Hunt DF, Engelhard VH, and Slingluff CL, Human melanoma patients recognize an HLA-Al-restricted CTL epitope from tyrosinase containing two cysteine residues: Implications for tumor vaccine development. J Immunol, 1998; 160: 2099–2106.

    PubMed  CAS  Google Scholar 

  7. Eder M, Battmer K, Kafert S, Stucki A, Ganser A, and Hertenstein B, Monitoring of BCR-ABL expression using real-time RT-PCR in CML after bone marrow or peripheral blood stem cell transplantation. Leukemia, 1999; 13: 1383–1389.

    Article  PubMed  CAS  Google Scholar 

  8. Osarogiagbon UR and McGlave PB, Chronic myelogenous leukaemia Current Opinion in Haematology, 1999; 6: 241–246.

    Article  CAS  Google Scholar 

  9. Boon T, Cerottini JC, Vandeneynde B, Vanderbruggen P, and Vanpel A, Tumor antigens recognized by T lymphocytes. Annu Rev Immunol, 1994; 12: 337–365.

    Article  PubMed  CAS  Google Scholar 

  10. Vanderbruggen P, Traversai C, Chomez P, Lurquin C, Deplaen E, Vandeneynde B, Knuth A, and Boon T, A gene encoding an antigen recognized by cytolytic lymphocytes-t on a human-melanoma Science, 1991; 254: 1643–1647.

    CAS  Google Scholar 

  11. Brichard V, Vanpel A, Wolfel T, Wolfel C, Deplaen E, Lethe B, Coulie P, and Boon T, The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med, 1993; 178: 489–495.

    Article  PubMed  CAS  Google Scholar 

  12. Kawakami Y, Eliyahu S, Sakaguchi K, Robbins PF, Rivoltini L, Yannelli JR, Appella E, and Rosenberg SA, Identification of the immunodominant peptides of the MART-1 human-melanoma antigen recognized by the majority of HLA-A2-restricted tumor-infiltrating lymphocytes. J Exp Med, 1994; 180: 347–352.

    Article  PubMed  CAS  Google Scholar 

  13. Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Sakaguchi K, Appella E, Yannelli JR, Adema GJ, Miki T, and Rosenberg SA, Identification of a human-melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in-vivo tumor rejection. Proc Natl Acad Sci U S A, 1994; 91: 6458–6462.

    Article  PubMed  CAS  Google Scholar 

  14. Schwartz RH, Immunological Tolerance, in Fundamental Immunology. 1993, Raven Press: New York. p. 677.

    Google Scholar 

  15. Linsley PS and Ledbetter JA, The role of the cd28 receptor during t-cell responses to antigen. Annu Rev Immunol, 1993; 11: 191–212.

    Article  PubMed  CAS  Google Scholar 

  16. Rocken M and Shevach EM, Immune deviation–The third dimension of nondeletional T cell tolerance. Immunol Rev, 1996; 149: 175–194.

    Article  PubMed  CAS  Google Scholar 

  17. Fruh K, Gruhler A, Krishna RM, and Schoenhals GJ, A comparison of viral immune escape strategies targeting the MHC class I assembly pathway. Immunol Rev, 1999; 168: 157–166.

    Article  PubMed  CAS  Google Scholar 

  18. Lee PP, Yee C, Savage PA, Fong L, Brockstedt D, Weber JS, Johnson D, Swetter S, Thompson J, Greenberg PD, Roederer M, and Davis MM, Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nat Med, 1999; 5: 677–685.

    Article  PubMed  CAS  Google Scholar 

  19. Skipper JCA, Gulden PH, Hendrickson RC, Harthun N, Caldwell JA, Shabanowitz J, Engelhard VH, Hunt DF, and Slingluff CL, Mass-spectrometric evaluation of HLA-A*0201-associated peptides identifies dominant naturally processed forms of CTL epitopes from MART-I and gp100. Int J Cancer, 1999; 82: 669–677.

    Article  PubMed  CAS  Google Scholar 

  20. Takashima A and Morita A, Dendritic cells in genetic immunization. J Leukoc Biol, 1999; 66: 350356.

    Google Scholar 

  21. Mommaas AM, Mulder AA, Jordens R, Out C, Tan MCAA, Cresswell P, Kluin PM, and Koning F, Human epidermal Langerhans cells lack functional mannose receptors and a fully developed endosomalllysosomal compartment for loading of HLA class II molecules. Eur J Immunol, 1999; 29: 571–580.

    Article  PubMed  CAS  Google Scholar 

  22. Rees RC and Mian S, Selective MHC expression in tumours modulates adaptive and innate antitumour responses. Cancer Immunology Immunotherapy, 1999; 48: 374–381.

    Article  CAS  Google Scholar 

  23. Sallusto F, Cella M, Danieli C, and Lanzavecchia A, Dendritic Cells Use Macropinocytosis and the Mannose Receptor to Concentrate Macromolecules In the Major Histocompatibility Complex Class-Ii Compartment - Down-Regulation By Cytokines and Bacterial Products. J Exp Med, 1995; 182: 389400.

    Google Scholar 

  24. Lutz MB, Rovere P, Kleijmeer MJ, Rescigno M, Assmann CU, Oorschot VMJ, Geuze HJ, Trucy J, Demandolx D, Davoust J, and RicciardiCastagnoli P, Intracellular routes and selective retention of antigens in mildly acidic cathepsin D/lysosome-associated membrane protein-1/MHC class II-positive vesicles in immature dendritic cells. J Immunol, 1997; 159: 3707–3716.

    PubMed  CAS  Google Scholar 

  25. Engering AJ, Cella M, Fluitsma D, Brockhaus M, Hoefsmit ECM, Lanzavecchia A, and Pieters J, The mannose receptor functions as a high capacity and broad specificity antigen receptor in human dendritic cells. Eur J Immunol, 1997; 27: 2417–2425.

    Article  PubMed  CAS  Google Scholar 

  26. Tan MCAA, Mommaas AM, Drijfhout JW, Jordens R, Onderwater JJM, Verwoerd D, Mulder AA, vanderHeiden AN, OttenhoffTHM, Cella M, Tulp A, Neefjes JJ, and Koning F, Mannose receptor mediated uptake of antigens strongly enhances HLA-class II restricted antigen presentation by cultured dendritic cells. Adv Exp Med Biol, 1997; 417: 171–174.

    PubMed  CAS  Google Scholar 

  27. Stahl PD and Ezekowitz RAB, The mannose receptor is a pattern recognition receptor involved in host defense. Curr Opin Immunol, 1998; 10: 50–55.

    Article  PubMed  CAS  Google Scholar 

  28. Kleijmeer MJ, Ossevoort MA, Vanveen CJH, Vanhellemond JJ, Neefjes JJ, Kast WM, Melief CJM, and Geuze HJ, MHC class-II compartments and the kinetics of antigen presentation in activated mouse spleen dendritic cells. J Immunol, 1995; 154: 5715–5724.

    PubMed  CAS  Google Scholar 

  29. Engering AJ, Cella M, Fluitsma DM, Hoefsmit ECM, Lanzavecchia A, and Pieters J, Mannose receptor mediated antigen uptake and presentation in human dendritic cells. Adv Exp Med Biol, 1997; 417: 183–187.

    PubMed  CAS  Google Scholar 

  30. Maurer D, Fiebiger E, Ebner C, Reininger B, Fischer GF, Wichlas S, Jouvin MH, SchmittEgenolf M, Kraft D, Kinet JP, and Stingl G, Peripheral blood dendritic cells express Fc epsilon RI as a complex composed of Fc epsilon RI alpha-and Fc epsilon RI gamma-chains and can use this receptor for IgEmediated allergen presentation. 1 Immunol, 1996; 157: 607–616.

    CAS  Google Scholar 

  31. Regnault A, Lankar D, Lacabanne V, Rodriguez A, Thery C, Rescigno M, Saito T, Verbeek S, Bonnerot C, RicciardiCastagnoli P, and Amigorena S, Fc gamma receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization. J Exp Med, 1999; 189: 371–380.

    Article  PubMed  CAS  Google Scholar 

  32. Brossart P and Bevan MJ, Presentation of exogenous protein antigens on major histocompatability complex class I molecules by dendritic cells: Pathway of presentation and regulation by cytokines. Blood, 1997; 90: 1594–1599.

    PubMed  CAS  Google Scholar 

  33. Huang AYC, Bruce AT, Pardoll DM, and Levitsky HI, In-Vivo Cross-Priming Of Mhc Class-I–Restricted Antigens Requires the Tap Transporter. Immunity, 1996; 4: 349–355.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  35. Albert ML, Pearce SFA, Francisco LM, Sauter B, Roy P, Silverstein RL, and Bhardwaj N, Immature dendritic cells phagocytose apoptotic cells via alpha(v)beta(5) and CD36, and cross-present antigens to cytotoxic T lymphocytes. J Exp Med, 1998; 188: 1359–1368.

    Article  PubMed  CAS  Google Scholar 

  36. Ronchetti A, Rovere P, Iezzi G, Galati G, Heltai S, Protti MP, Garancini MP, Manfredi AA, Rugarli C, and Bellone M, Immunogenicity of apoptotic cells in vivo: Role of antigen load, antigen-presenting cells, and cytokines. J Immunol, 1999; 163: 130–136.

    PubMed  CAS  Google Scholar 

  37. Bennett SRM, Carbone FR, Karamalis F, Miller JFAP, and Heath WR, Induction of a CD8(+) cytotoxic T lymphocyte response by cross-priming requires cognate CD4(+) T cell help. J Exp Med, 1997; 186: 65–70.

    Article  PubMed  CAS  Google Scholar 

  38. Gromme M, Uytdehaag FGCM, Janssen H, Calafat J, vanBinnendijk RS, Kenter MJH, Tulp A, Verwoerd D, and Neefjes J, Recycling MHC class I molecules and endosomal peptide loading. Proc Natl Acad Sci U S A, 1999; 96: 10326–10331.

    Article  PubMed  CAS  Google Scholar 

  39. Herbst B, Kohler G, Mackensen A, Veelken H, Kulmburg P, Rosenthal FM, Schaefer HE, Mertelsmann R, Fisch P, and Lindemann A, In vitro differentiation of CD34(+) hematopoietic progenitor cells toward distinct dendritic cell subsets of the birbeck granule and MIIC-positive Langerhans cell and the interdigitating dendritic cell type. Blood, 1996; 88: 2541–2548.

    PubMed  CAS  Google Scholar 

  40. Bernhard H, Disis ML, Heimfeld S, Hand S, Gralow JR, and Cheever MA, Generation Of Immunostimulatory Dendritic Cells From Human CD34+ Hematopoietic Progenitor Cells Of the Bone-Marrow and Peripheral- Blood. Cancer Res, 1995; 55: 1099–1104.

    PubMed  CAS  Google Scholar 

  41. Allavena P, Piemonti L, Longoni D, Bernasconi S, Stoppacciaro A, Ruco L, and Mantovani A, IL-10 prevents the differentiation of monocytes to dendritic cells but promotes their maturation to macrophages. Eur J Immunol, 1998; 28: 359–369.

    Article  PubMed  CAS  Google Scholar 

  42. Cella M, Engering A, Pinet V, Pieters J, and Lanzavecchia A, Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells. Nature, 1997; 388: 782–787.

    Article  PubMed  CAS  Google Scholar 

  43. Cella M, Salio M, Sakakibara Y, Langen H, Julkunen I, and Lanzavecchia A, Maturation, activation, and protection of dendritic cells induced by double-stranded RNA. J Exp Med, 1999; 189: 821–829.

    Article  PubMed  CAS  Google Scholar 

  44. Watanabe M, Choudhry A, Berlan M, Singal A, Siwik E, Mohr S, and Fisher SA, Developmental remodeling and shortening of the cardiac outflow tract involves myocyte programmed cell death. Development, 1998; 125: 3809–3820.

    PubMed  CAS  Google Scholar 

  45. Frade JM and Barde YA, Genetic evidence for cell death mediated by nerve growth factor and the neurotrophin receptor p75 in the developing mouse retina and spinal cord. Development, 1999; 126: 683–690.

    PubMed  CAS  Google Scholar 

  46. Gumienny TL, Lambie E, Hartwieg E, Horvitz HR, and Hengartner MO, Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline. Development, 1999; 126: 1011–1022.

    PubMed  CAS  Google Scholar 

  47. Rovere P, Vallinoto C, Bondanza A, Crosti MC, Rescigno M, RicciardiCastagnoli P, Rugarli C, and Manfredi AA, Bystander apoptosis triggers dendritic cell maturation and antigen-presenting function. J Immunol, 1998; 161: 4467–4471.

    PubMed  CAS  Google Scholar 

  48. Matzinger P, Tolerance, danger, and the extended family. Annu Rev Immunol, 1994; 12: 991–1045.

    Article  PubMed  CAS  Google Scholar 

  49. Gallucci S, Lolkema M, and Matzinger P, Natural adjuvants: endogenous activators of dendritic cells. Nat Med, 1999; 5: 1249–1255.

    Article  PubMed  CAS  Google Scholar 

  50. Melcher A, Todryk S, Hardwick N, Ford M, Jacobson M, and Vile RG, Tumor immunogenicity is determined by the mechanism of cell death via induction of heat shock protein expression. Nat Med, 1998; 4: 581–587.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  52. Blachere NE, Li ZH, Chandawarkar RY, Suto R, Jaikaria NS, Basu S, Udono H, and Srivastava PK, Heat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity. J Exp Med, 1997; 186: 1315–1322.

    Article  PubMed  CAS  Google Scholar 

  53. Chandawarkar RY, Wagh MS, and Srivastava PK, The dual nature of specific immunological activity of tumor-derived gp96 preparations. J Exp Med, 1999; 189: 1437–1442.

    Article  PubMed  CAS  Google Scholar 

  54. Yedavelli SPK, Guo L, Daou ME, Srivastava PK, Mittelman A, and Tiwari RK, Preventive and therapeutic effect of tumor derived heat shock protein, gp96, in an experimental prostate cancer model. Int J Mol Med, 1999; 4: 243–248.

    PubMed  CAS  Google Scholar 

  55. Jaattela M, Escaping cell death: Survival proteins in cancer. Exp Cell Res, 1999; 248: 30–43.

    Article  PubMed  CAS  Google Scholar 

  56. Schoenberger SP, vanderVoort EIH, Krietemeijer GM, Offringa R, Melief CJM, and Toes REM, Cross-priming of CTL responses in vivo does not require antigenic peptides in the endoplasmic reticulum of immunizing cells. J Immunol, 1998; 161: 3808–3812.

    PubMed  CAS  Google Scholar 

  57. Suto R and Srivastava PK, A Mechanism For the Specific Immunogenicity Of Heat-Shock Protein-Chaperoned Peptides. Science, 1995; 269: 1585–1588.

    Article  PubMed  CAS  Google Scholar 

  58. Basu S and Srivastava PK, Calreticulin, a peptide-binding chaperone of the endoplasmic reticulum, elicits tumor-and peptide-specific immunity. J Exp Med, 1999; 189: 797–802.

    Article  PubMed  CAS  Google Scholar 

  59. Ganss R, Limmer A, Sacher T, Arnold B, and Hammerling GJ, Autoaggression and tumor rejection: it takes more than self-specific T-cell activation. Immunol Rev, 1999; 169: 263–272.

    Article  PubMed  CAS  Google Scholar 

  60. Slavik JM, Hutchcroft JE, and Bierer BE, CD28/CTLA-4 and CD80/CD86 families–Signaling and function. Immunol Res, 1999; 19: 1–24.

    Article  PubMed  CAS  Google Scholar 

  61. Bennett SRM, Carbone FR, Karamalis F, Flavell RA, Miller JFAP, and Heath WR, Help for cytotoxicT-cell responses is mediated by CD40 signalling Nature, 1998; 393: 478–480.

    CAS  Google Scholar 

  62. Ridge JP, DiRosa F, and Matzinger P, A conditioned dendritic cell can be a temporal bridge between a CD4(+) T-helper and a T-killer cell. Nature, 1998; 393: 474–478.

    Article  PubMed  CAS  Google Scholar 

  63. Schoenberger SP, Toes REM, vanderVoort EIH, Offringa R, and Melief CJM, T-cell help for cytotoxic T lymphocytes is mediated by CD4O-CD4OL interactions. Nature, 1998; 393: 480–483.

    Article  PubMed  CAS  Google Scholar 

  64. Bianchi R, Grohmann U, Vacca C, Belladonna ML, Fioretti MC, and Puccetti P, Autotrine IL-12 is involved in dendritic cell modulation via CD40 ligation. J Immunol, 1999; 163: 2517–2521.

    PubMed  CAS  Google Scholar 

  65. Ohshima Y, Tanaka Y, Tozawa H, Takahashi Y, Maliszewski C, and Delespesse G, Expression and function of OX40 ligand on human dendritic cells. J Immunol, 1997; 159: 3838–3848.

    PubMed  CAS  Google Scholar 

  66. Gramaglia I, Weinberg AD, Lemon M, and Croft M, Ox-40 ligand: A potent costimulatory molecule for sustaining primary CD4 T cell responses. J Immunol, 1998; 161: 6510–6517.

    PubMed  CAS  Google Scholar 

  67. Chen AI, McAdam AJ, Buhlmann JE, Scott S, Lupher MU, Greenfield EA, Baum PR, Fanslow WC, Calderhead DM, Freeman GJ, and Sharpe AH, OX40-ligand has a critical co-stimulatory role in dendritic cell:T cell interactions. Immunity, 1999; 11: 689–698.

    Article  PubMed  CAS  Google Scholar 

  68. Kopf M, Ruedl C, Schmitz N, Gallimore A, Lefrang K, Ecabert B, Odermatt B, and Bachmann MF, OX40 deficient mice are defective in Th cell proliferation but are competent in generating B cell and CTL responses. Immunity, 1999; 11: 699–708.

    Article  PubMed  CAS  Google Scholar 

  69. Ito N, Nakamura H, Tanaka Y, and Ohgi S, Lung carcinoma–Analysis of T helper type 1 and 2 cells and T cytotoxic type 1 and 2 cells by intracellular cytokine detection with flow cytometry. Cancer, 1999; 85: 2359–2367.

    Article  PubMed  CAS  Google Scholar 

  70. Asselin-Paturel C, Echchakir H, Carayol G, Gay F, Opolon P, Grunenwald D, Chouaib S, and MamiChouaib F, Quantitative analysis of Thl, Th2 and TGF-beta 1 cytokine expression in tumor, TIL and PBL of non-small cell lung cancer patients. Int J Cancer, 1998; 77: 7–12.

    Article  PubMed  CAS  Google Scholar 

  71. Elsasser-Beile U, Kolble N, Grussenmeyer T, SchultzeSeemann W, Wetterauer U, Gallati H, Monting JS, and vonKleist S, Thl and Th2 cytokine response patterns in leukocyte cultures of patients with urinary bladder, renal cell and prostate carcinomas. Tumor Biology, 1998; 19: 470–476.

    Article  PubMed  CAS  Google Scholar 

  72. Qin ZH, Richter G, Schuler T, Ibe S, Cao XT, and Blankenstein T, B cells inhibit induction of T cell-dependent tumor immunity. Nat Med, 1998; 4: 627–630.

    Article  PubMed  CAS  Google Scholar 

  73. Salgame P, Abrams JS, Clayberger C, Goldstein H, Convit J, Modlin RL, and Bloom BR, Differing lymphokine profiles of functional subsets of human cd4 and cd8 t-cell clones. Science, 1991; 254: 279–282.

    Article  PubMed  CAS  Google Scholar 

  74. Croft M, Carter L, Swain SL, and Dutton RW, Generation of polarized antigen-specific cd8 effector populations–reciprocal action of interleukin (il)-4 and il-12 in promoting type-2 versus type-1 cytokine profiles. J Exp Med, 1994; 180: 1715–1728.

    Article  PubMed  CAS  Google Scholar 

  75. Mosmann TR and Sad S, The expanding universe of T-cell subsets: Th 1, Th2 and more. Immunol Today, 1996; 17: 138–146.

    Article  PubMed  CAS  Google Scholar 

  76. Li L, Sad S, Kagi D, and Mosmann TR, CD8Tcl and Tc2 cells secrete distinct cytokine patterns in vitro and in vivo but induce similar inflammatory reactions. J Immunol, 1997; 158: 4152–4161.

    PubMed  CAS  Google Scholar 

  77. Seder RA and Paul WE, Acquisition of lymphokine-producing phenotype by cd4+ t-cells. Annu Rev Immunol, 1994; 12: 635–673.

    Article  PubMed  CAS  Google Scholar 

  78. Nakamura T, Lee RK, Nam SY, Podack ER, Bottomly K, and Flavell RA, Roles of IL-4 and IFNgamma in stabilizing the T helper cell type 1 and 2 phenotype. J Immunol, 1997; 158: 2648–2653.

    PubMed  CAS  Google Scholar 

  79. Gollob JA, Kawasaki H, and Ritz J, Interferon-gamma and interleukin-4 regulate T cell interleukin-12 responsiveness through the differential modulation of high-affinity interleukin-12 receptor expression. Eur J Immunol, 1997; 27: 647–652.

    Article  PubMed  CAS  Google Scholar 

  80. Tamada K, Harada M, Abe K, Li TL, Tada H, Once Y, and Nomoto K, Immunosuppressive activity of cloned natural killer (NK1.1(+)) T cells established from murine tumor-infiltrating lymphocytes. J Immunol, 1997; 158: 4846–4854.

    PubMed  CAS  Google Scholar 

  81. vonderWeid T, Beebe AM, Roopenian DC, and Coffman RL, Early production of IL-4 and induction of Th2 responses in the lymph node originate from an MHC class I-independent CD4(+)NK1.I(-)T cell population. J Immunol, 1996; 157: 4421–4427.

    CAS  Google Scholar 

  82. Inoue M, Minami M, Fujii Y, Matsuda H, Shirakura R, and Kido T, Granulocyte colony-stimulating factor and interleukin-6-producing lung cancer cell line, LCAM. J Surg Oncol, 1997; 64: 347–350.

    Article  PubMed  CAS  Google Scholar 

  83. Rincon M, Anguita J, Nakamura T, Fikrig E, and Flavell RA, Interleukin (IL)-6 directs the differentiation of IL-4-producing CD4(+) T cells. J Exp Med, 1997; 185: 461–469.

    Article  PubMed  CAS  Google Scholar 

  84. Bendelac A, Rivera MN, Park SH, and Roark JH, Mouse CD1-specific NK1 T cells: Development, specificity, and function. Annu Rev Immunol, 1997; 15: 535–562.

    Article  PubMed  CAS  Google Scholar 

  85. Schartonkersten T, Afonso LCC, Wysocka M, Trinchieri G, and Scott P, IL-12 is required for naturalkiller-cell activation and subsequent t-helper-I cell-development in experimental leishmaniasis. J Immunol, 1995; 154: 5320–5330.

    CAS  Google Scholar 

  86. Scharton T and Scott PA, Natural killer cells are a source of interferon gamma that drives differentiation of CD4 T cell subsets and induces early resistance to Leishmania major in mice. J Exp Med, 1993; 176: 567.

    Article  Google Scholar 

  87. Constant SL and Bottomly K, Induction of THl and TH2 CD4+ T cell responses: The alternative approaches. Annu Rev Immunol, 1997; 15: 297–322.

    Article  PubMed  CAS  Google Scholar 

  88. McKnight AJ, Perez VL, Shea CM, Gray GS, and Abbas AK, Costimulator dependence of lymphokine secretion by naive and activated cd4(+) t-lymphocytes from to transgenic mice. J Immunol, 1994; 152: 5220–5225.

    PubMed  CAS  Google Scholar 

  89. Hosken NA, Shibuya K, Heath AW, Murphy KM, and Ogarra A, The effect of antigen dose on cd4(+) t-helper cell phenotype development in a t-cell receptor-alpha-beta-transgenic model. J Exp Med, 1995; 182: 1579–1584.

    Article  PubMed  CAS  Google Scholar 

  90. Tsung K, Meko JB, Peplinski GR, Tsung YL, and Norton JA, IL-12 induces T helper 1-directed antitumor response. J Immunol, 1997; 158: 3359–3365.

    PubMed  CAS  Google Scholar 

  91. Aruga A, Aruga E, Tanigawa K, Bishop DK, Sondak VK, and Chang AE, Type 1 versus type 2 cytokine release by V beta T cell subpopulations determines in vivo antitumor reactivity–IL-10 mediates a suppressive role. J Immunol, 1997; 159: 664–673.

    PubMed  CAS  Google Scholar 

  92. Lee PP, Zeng DF, McCaulay AE, Chen YF, Geiler C, Umetsu DT, and Chao NJ, T helper 2-dominant antilymphoma immune response is associated with fatal outcome. Blood, 1997; 90: 1611–1617.

    PubMed  CAS  Google Scholar 

  93. Lowes MA, Bishop GA, Crotty K, Bametson RS, and Halliday GM, T helper 1 cytokine mRNA is increased in spontaneously regressing primary melanomas. J Invest Dermatol, 1997; 108: 914–919.

    Article  PubMed  CAS  Google Scholar 

  94. Kagamu H and Shu SY, Purification of L-selectin(low) cells promotes the generation of highly potent CD4 antitumor effector T lymphocytes. J Immunol, 1998; 160: 3444–3452.

    PubMed  CAS  Google Scholar 

  95. Mobley JL and Dailey MO, Regulation of adhesion molecule expression by cd8 t-cells invivo.1. Differential regulation of gp90me1–14 (lecam-1), pgp-1, lfa-1, and vla-4-alpha during the differentiation of cytotoxic lymphocytes-t induced by allografts. J Immunol, 1992; 148: 2348–2356.

    PubMed  CAS  Google Scholar 

  96. Mobley JL, Rigby SM, and Dailey MO, Regulation of adhesion molecule expression by CD8 t-cells in-vivo.2. Expression of I-selectin (CD62L) by memory cytolytic T-cells responding to minor histocompatibility antigens. J Immunol, 1994; 153: 5443–5452.

    PubMed  CAS  Google Scholar 

  97. Hou S and Doherty PC, Partitioning of responder CD8(+) t-cells in lymph-node and lung of mice with sendai virus pneumonia by lecam-1 and CD45rb phenotype. J Immunol, 1993; 150: 5494–5500.

    PubMed  CAS  Google Scholar 

  98. Andersson EC, Christensen JP, Marker O, and Thomsen AR, Changes in cell-adhesion molecule expression on T-cells associated with systemic virus-infection. J Immunol, 1994; 152: 1237–1245.

    PubMed  CAS  Google Scholar 

  99. Bradley LM, Duncan DD, Tonkonogy S, and Swain SL, Characterization of antigen-specific CD4+ effector T-cells invivo - immunization results in a transient population of met-14-, CD45rb-helper-cells that secretes interleukin-2 (il-2), il-3, il-4, and interferon-gamma. J Exp Med, 1991; 174: 547559.

    Google Scholar 

  100. Hu HM, Urba WJ, and Fox BA, Gene-modified tumor vaccine with therapeutic potential shifts tumor-specific T cell response from a type 2 to a type 1 cytokine profile. J Immunol, 1998; 161: 3033–3041.

    PubMed  CAS  Google Scholar 

  101. Dobrzanski MJ, Reome JB, and Dutton RW, Type 1 and type 2 CD8(+) effector T cell subpopulations promote long-term tumor immunity and protection to progressively growing tumor. J Immunol, 2000; 164: 916–925.

    PubMed  CAS  Google Scholar 

  102. Rodolfo M, Zilocchi C, Accornero P, Cappetti B, Arioli I, and Colombo MP, IL-4-transduced tumor cell vaccine induces immunoregulatory type 2 CD8 T lymphocytes that cure lung metastases upon adoptive transfer. J Immunol, 1999; 163: 1923–1928.

    PubMed  CAS  Google Scholar 

  103. Hung K, Hayashi R, LafondWalker A, Lowenstein C, Pardoll D, and Levitsky H, The central role of CD4(+) T cells in the antitumor immune response. J Exp Med, 1998; 188: 2357–2368.

    Article  PubMed  CAS  Google Scholar 

  104. Schuler T, Qin ZH, Ibe S, NobenTrauth N, and Blankenstein T, T helper cell type 1-associated and cytotoxic T lymphocyte-mediated tumor immunity is impaired in interleukin 4-deficient mice. J Exp Med, 1999; 189: 803–810.

    Article  PubMed  CAS  Google Scholar 

  105. Henkart P, Cytotoxic T lymphocytes, in Fundamental Immunology. 1999, Raven Press: New York. p. 1021

    Google Scholar 

  106. Winter H, Hu HM, Urba WJ, and Fox BA, Tumor regression after adoptive transfer of effector T cells is independent of perforin or Fas ligand (APO-1L/CD95L). J Immunol, 1999; 163: 4462–4472.

    PubMed  CAS  Google Scholar 

  107. Chu Y, Hu HM, Winter H, Wood WJ, Doran T, Lashley D, Bashey J, Schuster J, Wood J, Lowe BA, Vetto JT, Weinberg AD, Puri R, Smith JW, Urba WJ, and Fox BA, Examining the immune response in sentinel lymph nodes of mice and men. Eur J Nucl Med, 1999; 26: S50 - S53.

    Article  PubMed  CAS  Google Scholar 

  108. Murphy G, Tjoa B, Ragde H, Kenny G, and Boynton A, Phase I clinical trial: T-cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA-A0201-specific peptides from prostate-specific membrane antigen. Prostate, 1996; 29: 371–380.

    Article  PubMed  CAS  Google Scholar 

  109. Tjoa BA, Erickson SJ, Bowes VA, Ragde H, Kenny GM, Cobb 0E, Ireton RC, Troychak MJ, Boynton AL, and Murphy GP, Follow-up evaluation of prostate cancer patients infused with autologous dendritic cells pulsed with PSMA peptides. Prostate, 1997; 32: 272–278.

    Article  PubMed  CAS  Google Scholar 

  110. Salgaller ML, Lodge PA, McLean JG, Tjoa BA, Loftus DJ, Ragde H, Kenny GM, Rogers M, Boynton AL, and Murphy GP, Report of immune monitoring of prostate cancer patients undergoing T-cell therapy using dendritic cells pulsed with HLA-A2-specific peptides from prostate-specific membrane antigen (PSMA). Prostate, 1998; 35: 144–151.

    Article  PubMed  CAS  Google Scholar 

  111. Simmons SJ, Tjoa BA, Rogers M, Elgamal A, Kenny GM, Ragde H, Troychak Mil, Boynton AL, and Murphy GP, GM-CSF as a systemic adjuvant in a phase II prostate cancer vaccine trial. Prostate, 1999; 39: 291–297.

    Article  PubMed  CAS  Google Scholar 

  112. Nestle FO, Alijagic S, Gilliet M, Sun YS, Grabbe S, Dummer R, Burg G, and Schadendorf D, Vaccination of melanoma patients with peptide-or tumor lysate-pulsed dendritic cells. Nat Med, 1998; 4: 328–332.

    Article  PubMed  CAS  Google Scholar 

  113. Hsu FJ, Benike C, Fagnoni F, Liles TM, Czerwinski D, Taidi B, Engleman EG, and Levy R, Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med, 1996; 2: 52–58.

    Article  PubMed  CAS  Google Scholar 

  114. Diehl L, denBoer AT, Schoenberger SP, vanderVoort EIH, Schumacher TNM, Melief CJM, Offringa R, and Toes REM, CD40 activation in vivo overcomes peptide-induced peripheral cytotoxic T- lymphocyte tolerance and augments anti-tumor vaccine efficacy. Nat Med, 1999; 5: 774–779.

    Article  PubMed  CAS  Google Scholar 

  115. Chaux P, Vantomme V, Stroobant V, Thielemans K, Corthals J, Luiten R, Eggermont AMM, Boon T, and vanderBruggen P, Identification of MAGE-3 epitopes presented by HLA-DR molecules to CD4(+) T lymphocytes. J Exp Med, 1999; 189: 767–777.

    Article  PubMed  CAS  Google Scholar 

  116. Wu TC, Guamieri FG, Staveleyocarroll KF, Viscidi RP, Levitsky HI, Hedrick L, Cho KR, August JT, and Pardoll DM, Engineering an intracellular pathway for major histocompatibility complex class-ii presentation of antigens. Proc Natl Acad Sci U S A, 1995; 92: 11671–11675.

    Article  PubMed  CAS  Google Scholar 

  117. Lin KY, Guarnieri FG, Staveleyocarroll KF, Levitsky HI, August 1T, Pardoll DM, and Wu TC, Treatment Of Established Tumors With a Novel Vaccine That Enhances Major Histocompatibility Class-li Presentation Of Tumor-Antigen. Cancer Res, 1996; 56: 21–26.

    PubMed  CAS  Google Scholar 

  118. Rodriguez F, An LL, Harkins S, Zhang J, Yokoyama M, Widera G, Fuller JT, Kincaid C, Campbell IL, and Whitton JL, DNA immunization with minigenes: Low frequency of memory cytotoxic T lymphocytes and inefficient antiviral protection are rectified by ubiquitination. J Virol, 1998; 72: 5174–5181.

    PubMed  CAS  Google Scholar 

  119. Yu ZY, Karem KL, Kanangat S, Manickan E, and Rouse BT, Protection by minigenes: a novel approach of DNA vaccines. Vaccine, 1998; 16: 1660–1667.

    Article  PubMed  CAS  Google Scholar 

  120. Ishioka GY, Fikes J, Hermanson G, Livingston B, Crimi C, Qin MS, delGuercio MF, Oseroff C, Dahlberg C, Alexander J, Chesnut RW, and Sette A, Utilization of MHC class I transgenic mice for development of minigene DNA vaccines encoding multiple HLA-restricted CTL epitopes. J Immunol, 1999; 162: 3915–3925.

    PubMed  CAS  Google Scholar 

  121. Iwasaki A, DelaCruz CS, Young AR, and Barber BH, Epitope-specific cytotoxic T lymphocyte induction by minigene DNA immunization. Vaccine, 1999; 17: 2081–2088.

    Article  PubMed  CAS  Google Scholar 

  122. Petersen TR, Bregenholta S, Pedersen LO, Nissen MH, and Claesson MH, Human p53(264–272) HLAA2 binding peptide is an immunodominant epitope in DNA-immunized HLA-A2 transgenic mice. Cancer Lett, 1999; 137: 183–191.

    Article  PubMed  CAS  Google Scholar 

  123. Zitvogel L, Regnault A, Lozier A, Wolfers J, Flament C, Tenza D, RicciardiCastagnoli P, Raposo G, and Amigorena S, Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat Med, 1998; 4: 594–600.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Shahid Mian
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  2. R. Adrian Robins
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  3. Robert C. Rees
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  4. Bernie Fox
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Editors and Affiliations

  1. Division of Immunology, Nottingham University Queen’s Medical Centre, Nottingham, UK

    R. Adrian Robins

  2. Department of Life Sciences, The Nottingham Trent University, Nottingham, UK

    Robert C. Rees

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Mian, S., Robins, R.A., Rees, R.C., Fox, B. (2001). Immunogenicity of tumour associated antigens. In: Robins, R.A., Rees, R.C. (eds) Cancer Immunology. Immunology and Medicine Series, vol 30. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-0963-7_1

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  • DOI: https://doi.org/10.1007/978-94-017-0963-7_1

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