Advertisement

T Cell-Mediated Tumor Regression in Experimental Systems

  • R. J. North
  • M. Awwad
  • P. L. Dunn

Abstract

It was established in the 1950s and 60s (Old and Boyce 1964; Sjögren 1965; Klein 1966; Hellström and Hellström 1969) that murine tumors can possess transplantation rejection antigens capable of evoking an antitumor immune response in their syngeneic hosts. It was also established that antitumor immunity is cell-mediated. In the 1970s a great deal of effort led to the realization that, in spite of their possession of rejection antigens, immunogenic tumors are highly resistant to attempts to cause their regression by immunotherapeutic modalities that employ immunoadjuvants (Bast et al. 1976). Consequently examples of successful active immunotherapy of immunogenic tumors are rare. In contrast, it has become almost routine to cause the regression of established murine tumors by adoptive immunization with immune T cells from immunized donors. The convincing success of adoptive immunotherapy serves to demonstrate that immunogenic tumors fail to undergo regression because of a shortfall in host effector lymphocytes, rather than because of some tumor-mediated anti- host mechanism that blocks the expression of immunity. It is perhaps time again, therefore, to work at discovering ways to stimulate the host itself to produce therapeutic numbers of effector lymphocytes, rather than to supply it with T cells from immune donors, or with tumor-infiltrating lymphocytes expanded in number in vitro. It will be argued here that, in order for anti-tumor immunity to be augmented to a therapeutic level, it is necessary, in the case of some tumors, to remove the negative regulatory influence of tumor-induced suppressor T cells. Indeed, it needs to be realized that removing the influence of suppressor cells is also a prerequisite for successful adoptive immunotherapy as practiced at present.

Keywords

Antitumor Immunity Antitumor Immune Response Adoptive Immunotherapy Tumor Bearer Immunogenic Tumor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Awwad M, North RJ (1987) Cyclophosphamide (Cy)-facilitated adoptive immunotherapy of a Cy-resistant tumor. Evidence that Cy permits the expression of adoptive T cell-mediated immunity by removing suppressor T cells rather than by reducing tumor burden. Immunology 65:87–92Google Scholar
  2. Awwad M, North RJ (1988) Immunologically mediated regression of a murine lymphoma after treatment with anti-L3T4 antibody. A consequence of removing L3T4+ suppressor T cells from a host generating predominantly Lyt-2+ T cell-mediated immunity. J Exp Med 168:2193–2206PubMedCrossRefGoogle Scholar
  3. Awwad M, North RJ (1989) Cyclophosphamide-induced immunologically mediated regression of a cyclophosphamide-resistant murine tumor: A consequence of eliminating precursor L3T4+ suppressor T cells. Cancer Res 49:1649–1654PubMedGoogle Scholar
  4. Bast RC, Bast BC, Rapp HJ (1976) Critical reviews of previously reported animal studies of tumor immunotherapy with non-specific immunostimulants. Ann NY Acad Sci 277:60–92PubMedCrossRefGoogle Scholar
  5. Hellstrttm KE, Hellstrom I (1969) Cellular immunity against tumor antigens. Adv Cancer Res 12:167–223CrossRefGoogle Scholar
  6. Hill JO, Awwad M, North RJ (1989) Elimination of CD4+ suppressor T cells from susceptible BALB/c mice releases CD8+ T lymphocytes to mediate protective immunity against Leishmanias. J Exp Med 169:1819–1828PubMedCrossRefGoogle Scholar
  7. Klein G (1966) Tumor antigens. Ann Rev Microbiol 20:223–252CrossRefGoogle Scholar
  8. Mokyr MB, Baker E (1986) Specificity of the generation and expression of enhanced anti-plasmacytoma immunity by spleen cells from melphalan- treated MOPC-315 tumor bearers. Cancer Immunol Immunother 23:11–19PubMedCrossRefGoogle Scholar
  9. North RJ (1982) Cyclophosphamide-facilitated adoptive immunotherapy of an established tumor depends on elimination of tumor-induced suppressor T cells. J Exp Med 55:1063–1074CrossRefGoogle Scholar
  10. North RJ (1984a) γ-Irradiation facilitates the expression of adoptive immunity against established tumors by eliminating suppressor T cells. Cancer Immunol Immunother 16:175–181PubMedCrossRefGoogle Scholar
  11. North RJ (1984b) The therapeutic significance of concomitant antitumor immunity. I. Ly-l-2+ T cells from mice with a progressive tumor can cause regression of an established tumor in γ-irradiated recipients. Cancer Immunol Immunother 18:69–74PubMedCrossRefGoogle Scholar
  12. North RJ (1985) Down regulation of the antitumor immune response. Adv Cancer Res 45:1–4 3Google Scholar
  13. North RJ, Bursuker I (1984) The generation and decay of the immune response to a progressive fibrosarcoma. 1. Ly-l+2” suppressor T cells down-regulate the generation of Ly-1+2+ effector T cells. J Exp Med 159:1295–1311PubMedCrossRefGoogle Scholar
  14. North RJ, Dye ES (1985) Ly-l+2- suppressor T cells down-regulate the generation of Ly-1-2+ effector T cells during progressive growth of the P815 mastocytoma. Immunology 54:47–56PubMedCentralPubMedGoogle Scholar
  15. Old U, Boyse EA (1964) Immunology of experimental tumors. Ann Rev Med 15:167–186PubMedCrossRefGoogle Scholar
  16. Pearce NW, Spinelli A, Gurley KE, Dorsch SE, Hall BM (1989) Mechanisms maintaining antibody-induced enhancement of allografts. II. Mediation of specific suppression by short lived CD4+ T cells. J Immunol 143:499–506PubMedGoogle Scholar
  17. Quigley RL, Wood KJ, Morris PJ (1989) Mediation of antigen-induced suppression of renal allograft rejection by a CD4 (W3/25+) T cell. Transplantation 47:689–695PubMedCrossRefGoogle Scholar
  18. Rosenberg SA, Spiess P, Lafreniere R (1986) A new approach to the adoptive immunotherapy of cancer using tumor infiltrating lymphocytes. Science 233:1318–1320PubMedCrossRefGoogle Scholar
  19. Sjögren HO (1965) Transplantation methods as a tool for detection of tumor-specific antigens. Prog Exp Tumor Res 6:189–322Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • R. J. North
  • M. Awwad
  • P. L. Dunn

There are no affiliations available

Personalised recommendations