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The antitumor immune response as a problem of self-nonself discrimination: Implications for immunotherapy

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Much evidence now exists that tumors possess specific antigens recognizable by T cells. The goal of immunotherapy is to break tolerance to these antiens while preserving self-tolerance. Recently, newer approaches have been developed in animal systems that modify tumor cells genetically so that they express new antigens or secrete certain cytokines. Engineering tumor cells to secrete cytokines in a paracrine fashion can induce powerful local cytokine effects which, in addition to inducing local inflammation, can alter the presentation of tumor antigens or the activation of tumor-antigen-specific T lymphocytes, resulting in systemic antitumor immunity.

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References

  1. Germain RN: Immunology: The ins and outs of antigen processing and presentation. Nature 1986;322:687–689.

    Article  PubMed  CAS  Google Scholar 

  2. Lurquin C, Van Pel A, Mariame B, De Plaen E, Szikara JP, Janssens C, Reddehase M, Lejeune J, Boon T: Structure of the gene of tum− transplantation antigen P91A: The mutated exon encodes a peptide recognized with Ld by cytolytic T cells. Cell 1989;58:293–303.

    Article  PubMed  CAS  Google Scholar 

  3. Hunter T: Cooperation between oncogenes. Cell 1991;64:249–270.

    Article  PubMed  CAS  Google Scholar 

  4. Marshall CJ: Tumor suppressor genes. Cell 1991;64:313–326.

    Article  PubMed  CAS  Google Scholar 

  5. van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, van den Eynde B, Knuth A, Boon T: A gene encoding an antigen recognized cytotoxic T lymphocytes on a human melanoma. Science 1991; 254:1643–1648.

    Article  PubMed  Google Scholar 

  6. Zinkernagel RM, Callahan GN Althage A, Cooper S, Streilein JW, Klein J: The lymphoreticular system in triggering virus plus self-specific cytotoxic T cells: Evidence for T help. J Exp Med 1978;147:897–911.

    Article  PubMed  CAS  Google Scholar 

  7. von Boehmer H, Haas W: Distinct Ir genes for helper and killer cells in the cytotoxic response to H-Y antigen. J Exp Med 1979;150:1134–1142.

    Article  Google Scholar 

  8. Keene J, Forman J: Helper activity is required for the in vivo generation of cytotoxic T lymphocytes. J Exp Med 1982;155:768–782.

    Article  PubMed  CAS  Google Scholar 

  9. Linsley PS, Clark EA, Ledbetter J: T-cell antigen CD28 mediates adhesion with B cells by interacting with activation antigen B7/BB-1. Proc Natl Acad Sci USA 1990;87:5031–5035.

    Article  PubMed  CAS  Google Scholar 

  10. Fearon E, Pardoll D, Itaya T, Golumbek P, Levitsky H, Simons J, Karasuyama H, Vogelstein B, Frost P: Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell 1990;60:397–403.

    Article  PubMed  CAS  Google Scholar 

  11. Jenkins MK, Pardoll DM, Mizuguchi J, Chused TM, Schwartz RH: Molecular events in the induction of a nonresponsive state in interleukin-2-producing helper T-lymphocyte clones. Proc Natl Acad Sci USA 1987;84:5409.

    Article  PubMed  CAS  Google Scholar 

  12. Jenkins MK, Pardoll DM, Mizuguchi J, Quill H, Schwartz RH: T-cell unresponsiveness in vivo and in vitro: Fine specificity of induction and molecular characterization of the unresponsive state. Immunol Rev 1987;95:113.

    Article  PubMed  CAS  Google Scholar 

  13. Gaspari A, Jenkins M, Katz S: Class II MHC-bearing keratinocytes induce antigen-specific unresponsiveness in hapten-specific TH1 clones. J Immunol 1988;141:2216–2220.

    PubMed  CAS  Google Scholar 

  14. Lo D, Burkly L, Widera G, Cowing C, Flavell R, Palmiter R, Brinster R: Diabetes and tolerance in transgenic mice expressing class II MHC molecules in pancreatic beta cells. Cell 1988;53:159–168.

    Article  PubMed  CAS  Google Scholar 

  15. Markmann J, Lo D, Naji A, Palmiter R, Brinster R, Heber-Katz E: Antigen presenting function of class II MHC expressing pancreatic beta cells. Nature 1988;336:476.

    Article  PubMed  CAS  Google Scholar 

  16. Fernandez-Botran R, et al: Interleukin 4 mediates autocrine growth of helper T cells after antigenic stimulation. Proc Natl Acad Sci USA 1986;83:9689–9693.

    Article  PubMed  CAS  Google Scholar 

  17. Hu-Li J, et al: B cell stimulatory factor 1 (interleukin 4) is a potent costimulant for normal resting T lymphocytes. J Exp Med 1987;165:157–172.

    Article  PubMed  CAS  Google Scholar 

  18. Widmer M, Grabstein K: Regulation of cytolytic T-lymphocyte generation by B-cell stimulatory factor. Nature 1987;326:795–798.

    Article  PubMed  CAS  Google Scholar 

  19. Trenn G, Takayama H, Hu-Li J, Paul WE, Sitkovsky MV: B cell stimulatory factor 1 (IL-4) enhances the development of cytotoxic T cells from Lyt-2+ resting murine T lymphocytes. J Immunol 1988;140: 1101–1106.

    PubMed  CAS  Google Scholar 

  20. Grusby MJ, et al: Cloning of an interleukin 4 inducible gene from cytotoxie T lymphocytes and its identification as a lipase. Cell 1990; 60:451.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Oncology, Medicine and Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 364, 21205-2196, Baltimore, Md., USA

    Paul Golumbek, Hy Levitsky, Liz Jaffee & Drew M. Pardoll

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  1. Paul Golumbek
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  2. Hy Levitsky
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  3. Liz Jaffee
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  4. Drew M. Pardoll
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Golumbek, P., Levitsky, H., Jaffee, L. et al. The antitumor immune response as a problem of self-nonself discrimination: Implications for immunotherapy. Immunol Res 12, 183–192 (1993). https://doi.org/10.1007/BF02918303

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