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. 1988 Apr;8(4):1857–1861. doi: 10.1128/mcb.8.4.1857

Rejection of B16 melanoma induced by expression of a transfected major histocompatibility complex class I gene.

K Tanaka 1, E Gorelik 1, M Watanabe 1, N Hozumi 1, G Jay 1
PMCID: PMC363355  PMID: 3380102

Abstract

Transfection of a functional major histocompatibility complex class I gene into certain tumor cells, induced by oncogenic viruses or chemical carcinogens, can effectively abrogate their tumorigenic activity. Since experimentally induced tumors possess strong tumor-specific transplantation antigens, expression of cell surface class I antigens may present the tumor cells to appropriate immune effector cells. Most spontaneously arising tumors do not possess tumor-specific transplantation antigens, and their tumorigenicity may not be affected by the expression of a transfected class I gene. We demonstrate that the poorly immunogenic B16-BL6 melanoma can be rendered nontumorigenic in syngeneic mice by the expression of the class I H-2K antigen but not the class II I-A antigen. Furthermore, the poorly tumorigenic, class I-expressing B16-BL6-transfected cells can effectively immunize syngeneic C57BL/6 mice against the highly tumorigenic, class I-deficient B16-BL6 parental cells. Our success in experimentally manipulating the tumorigenicity of a spontaneously derived neoplasm offers hope for a potential modality for the effective treatment of human cancer.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersson M., Päbo S., Nilsson T., Peterson P. A. Impaired intracellular transport of class I MHC antigens as a possible means for adenoviruses to evade immune surveillance. Cell. 1985 Nov;43(1):215–222. doi: 10.1016/0092-8674(85)90026-1. [DOI] [PubMed] [Google Scholar]
  2. Bernards R., Dessain S. K., Weinberg R. A. N-myc amplification causes down-modulation of MHC class I antigen expression in neuroblastoma. Cell. 1986 Dec 5;47(5):667–674. doi: 10.1016/0092-8674(86)90509-x. [DOI] [PubMed] [Google Scholar]
  3. Burgert H. G., Kvist S. An adenovirus type 2 glycoprotein blocks cell surface expression of human histocompatibility class I antigens. Cell. 1985 Jul;41(3):987–997. doi: 10.1016/s0092-8674(85)80079-9. [DOI] [PubMed] [Google Scholar]
  4. Cosman D., Kress M., Khoury G., Jay G. Tissue-specific expression of an unusual H-2 (class I)-related gene. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4947–4951. doi: 10.1073/pnas.79.16.4947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. De Baetselier P., Katzav S., Gorelik E., Feldman M., Segal S. Differential expression of H-2 gene products in tumour cells in associated with their metastatogenic properties. Nature. 1980 Nov 13;288(5787):179–181. doi: 10.1038/288179a0. [DOI] [PubMed] [Google Scholar]
  6. Doherty P. C., Knowles B. B., Wettstein P. J. Immunological surveillance of tumors in the context of major histocompatibility complex restriction of T cell function. Adv Cancer Res. 1984;42:1–65. doi: 10.1016/s0065-230x(08)60455-8. [DOI] [PubMed] [Google Scholar]
  7. Festenstein H., Schmidt W. Variation in MHC antigenic profiles of tumor cells and its biological effects. Immunol Rev. 1981;60:85–127. doi: 10.1111/j.1600-065x.1981.tb00363.x. [DOI] [PubMed] [Google Scholar]
  8. Fidler I. J., Gersten D. M., Hart I. R. The biology of cancer invasion and metastasis. Adv Cancer Res. 1978;28:149–250. doi: 10.1016/s0065-230x(08)60648-x. [DOI] [PubMed] [Google Scholar]
  9. Gooding L. R. Characterization of a progressive tumor from C3H fibroblasts transformed in vitro with SV40 virus. Immunoresistance in vivo correlates with phenotypic loss of H-2Kk. J Immunol. 1982 Sep;129(3):1306–1312. [PubMed] [Google Scholar]
  10. Gorelik E., Peppoloni S., Overton R., Herberman R. B. Increase in H-2 antigen expression and immunogenicity of BL6 melanoma cells treated with N-methyl-N'-nitronitrosoguanidine. Cancer Res. 1985 Nov;45(11 Pt 1):5341–5347. [PubMed] [Google Scholar]
  11. Hart I. R. The selection and characterization of an invasive variant of the B16 melanoma. Am J Pathol. 1979 Dec;97(3):587–600. [PMC free article] [PubMed] [Google Scholar]
  12. Hayashi H., Tanaka K., Jay F., Khoury G., Jay G. Modulation of the tumorigenicity of human adenovirus-12-transformed cells by interferon. Cell. 1985 Nov;43(1):263–267. doi: 10.1016/0092-8674(85)90031-5. [DOI] [PubMed] [Google Scholar]
  13. Hewitt H. B., Blake E. R., Walder A. S. A critique of the evidence for active host defence against cancer, based on personal studies of 27 murine tumours of spontaneous origin. Br J Cancer. 1976 Mar;33(3):241–259. doi: 10.1038/bjc.1976.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hui K., Grosveld F., Festenstein H. Rejection of transplantable AKR leukaemia cells following MHC DNA-mediated cell transformation. Nature. 1984 Oct 25;311(5988):750–752. doi: 10.1038/311750a0. [DOI] [PubMed] [Google Scholar]
  15. Jennings S. R., Rice P. L., Kloszewski E. D., Anderson R. W., Thompson D. L., Tevethia S. S. Effect of herpes simplex virus types 1 and 2 on surface expression of class I major histocompatibility complex antigens on infected cells. J Virol. 1985 Dec;56(3):757–766. doi: 10.1128/jvi.56.3.757-766.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kress M., Liu W. Y., Jay E., Khoury G., Jay G. Comparison of class I (H-2) gene sequences. Derivation of unique probes for members of this multigene family. J Biol Chem. 1983 Nov 25;258(22):13929–13936. [PubMed] [Google Scholar]
  17. Meruelo D., Kornreich R., Rossomando A., Pampeno C., Boral A., Silver J. L., Buxbaum J., Weiss E. H., Devlin J. J., Mellor A. L. Lack of class I H-2 antigens in cells transformed by radiation leukemia virus is associated with methylation and rearrangement of H-2 DNA. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4504–4508. doi: 10.1073/pnas.83.12.4504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Oi V. T., Jones P. P., Goding J. W., Herzenberg L. A., Herzenberg L. A. Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens. Curr Top Microbiol Immunol. 1978;81:115–120. doi: 10.1007/978-3-642-67448-8_18. [DOI] [PubMed] [Google Scholar]
  19. Pierres M., Devaux C., Dosseto M., Marchetto S. Clonal analysis of B- and T-cell responses to Ia antigens. I. Topology of epitope regions on I-Ak and I-Ek molecules analyzed with 35 monoclonal alloantibodies. Immunogenetics. 1981 Dec;14(6):481–495. doi: 10.1007/BF00350120. [DOI] [PubMed] [Google Scholar]
  20. Rogers M. J., Gooding L. R., Margulies D. H., Evans G. A. Analysis of a defect in the H-2 genes of SV40 transformed C3H fibroblasts that do not express H-2Kk. J Immunol. 1983 May;130(5):2418–2422. [PubMed] [Google Scholar]
  21. Schrier P. I., Bernards R., Vaessen R. T., Houweling A., van der Eb A. J. Expression of class I major histocompatibility antigens switched off by highly oncogenic adenovirus 12 in transformed rat cells. 1983 Oct 27-Nov 2Nature. 305(5937):771–775. doi: 10.1038/305771a0. [DOI] [PubMed] [Google Scholar]
  22. Tanaka K., Hayashi H., Hamada C., Khoury G., Jay G. Expression of major histocompatibility complex class I antigens as a strategy for the potentiation of immune recognition of tumor cells. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8723–8727. doi: 10.1073/pnas.83.22.8723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tanaka K., Isselbacher K. J., Khoury G., Jay G. Reversal of oncogenesis by the expression of a major histocompatibility complex class I gene. Science. 1985 Apr 5;228(4695):26–30. doi: 10.1126/science.3975631. [DOI] [PubMed] [Google Scholar]
  24. Tanaka K., Yoshioka T., Bieberich C., Jay G. Role of the major histocompatibility complex class I antigens in tumor growth and metastasis. Annu Rev Immunol. 1988;6:359–380. doi: 10.1146/annurev.iy.06.040188.002043. [DOI] [PubMed] [Google Scholar]
  25. Vaessen R. T., Houweling A., Israel A., Kourilsky P., van der Eb A. J. Adenovirus E1A-mediated regulation of class I MHC expression. EMBO J. 1986 Feb;5(2):335–341. doi: 10.1002/j.1460-2075.1986.tb04217.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Vaessen R. T., Houweling A., van der Eb A. J. Post-transcriptional control of class I MHC mRNA expression in adenovirus 12-transformed cells. Science. 1987 Mar 20;235(4795):1486–1488. doi: 10.1126/science.3823900. [DOI] [PubMed] [Google Scholar]
  27. Wallich R., Bulbuc N., Hämmerling G. J., Katzav S., Segal S., Feldman M. Abrogation of metastatic properties of tumour cells by de novo expression of H-2K antigens following H-2 gene transfection. Nature. 1985 May 23;315(6017):301–305. doi: 10.1038/315301a0. [DOI] [PubMed] [Google Scholar]
  28. Watanabe M., Shinohara N., Ochi A., Hozumi N. Functional reconstitution of class II major histocompatibility complex molecules, I-A alpha k and I-A beta k. Immunol Lett. 1986 Oct 15;13(5):237–244. doi: 10.1016/0165-2478(86)90108-2. [DOI] [PubMed] [Google Scholar]
  29. Weber J. S., Jay G., Tanaka K., Rosenberg S. A. Immunotherapy of a murine tumor with interleukin 2. Increased sensitivity after MHC class I gene transfection. J Exp Med. 1987 Dec 1;166(6):1716–1733. doi: 10.1084/jem.166.6.1716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Weiss E. H., Golden L., Fahrner K., Mellor A. L., Devlin J. J., Bullman H., Tiddens H., Bud H., Flavell R. A. Organization and evolution of the class I gene family in the major histocompatibility complex of the C57BL/10 mouse. Nature. 1984 Aug 23;310(5979):650–655. doi: 10.1038/310650a0. [DOI] [PubMed] [Google Scholar]

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