Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1984 Jun;81(11):3511–3515. doi: 10.1073/pnas.81.11.3511

T-cell-mediated cytotoxicity against autologous malignant melanoma: analysis with interleukin 2-dependent T-cell cultures.

A Knuth, B Danowski, H F Oettgen, L J Old
PMCID: PMC345538  PMID: 6610177

Abstract

The cytotoxic reactivity of lymphocytes for autologous melanoma cells was studied in a group of 13 melanoma patients. No cytotoxicity was observed with lymphocytes freshly isolated from peripheral blood or with lymphocytes cocultured for 7 days with autologous melanoma cells. Growth of lymphocytes previously sensitized with autologous melanoma in vitro in interleukin 2 (IL-2)-containing medium, however, resulted in cytotoxic reactivity for autologous melanoma in 7/13 patients. The reactivity of IL-2-dependent lymphocytes for autologous melanoma was particularly striking in one patient (A.V.) who has had an unexpectedly favorable clinical course and, because of their consistently high reactivity, AV lymphocytes were selected for detailed specificity analysis. After 2-3 weeks in culture in IL-2-containing medium, AV lymphocytes were cytolytic for autologous melanoma cells but not autologous Epstein-Barr virus-transformed B cells, autologous fibroblasts, or allogeneic tumor targets. Specificity of autologous melanoma reactivity was confirmed by competitive inhibition assays. The IL-2-dependent AV lymphocytes formed rosettes with sheep erythrocytes and expressed OKT 3 and Ia antigens. After longer periods of culture, AV lymphocytes were found to react with a wider range of target cells, and repeated attempts to isolate cultures with restricted reactivity to autologous melanoma by resensitization with autologous melanoma and limiting-dilution techniques were unsuccessful. The restricted reactivity of early cultures could be preserved, however, in frozen storage, but shifted again toward broader reactivity after several weeks in culture. The recognition of cytotoxic T cells with initial restricted reactivity for autologous melanoma suggests reinvestigation of the question of specific cellular immunity to human cancer.

Full text

PDF
3511

Selected References

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

  1. Albino A. P., Lloyd K. O., Houghton A. N., Oettgen H. F., Old L. J. Heterogeneity in surface antigen and glycoprotein expression of cell lines derived from different melanoma metastases of the same patient. Implications for the study of tumor antigens. J Exp Med. 1981 Dec 1;154(6):1764–1778. doi: 10.1084/jem.154.6.1764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Carey T. E., Takahashi T., Resnick L. A., Oettgen H. F., Old L. J. Cell surface antigens of human malignant melanoma: mixed hemadsorption assays for humoral immunity to cultured autologous melanoma cells. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3278–3282. doi: 10.1073/pnas.73.9.3278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Garrett T. J., Takahashi T., Clarkson B. D., Old L. J. Detection of antibody to autologous human leukemia cells by immune adherence assays. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4587–4590. doi: 10.1073/pnas.74.10.4587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gillis S., Smith K. A. Long term culture of tumour-specific cytotoxic T cells. Nature. 1977 Jul 14;268(5616):154–156. doi: 10.1038/268154a0. [DOI] [PubMed] [Google Scholar]
  5. Livingston P. O., Shiku H., Bean M. A., Pinsky C. M., Oettgen H. F., Old L. J. Cell-mediated cytotoxicity for cultured autologous melanoma cells. Int J Cancer. 1979 Jul 15;24(1):34–44. doi: 10.1002/ijc.2910240107. [DOI] [PubMed] [Google Scholar]
  6. Livingston P. O., Watanabe T., Shiku H., Houghton A. N., Albino A., Takahashi T., Resnick L. A., Michitsch R., Pinsky C. M., Oettgen H. F. Serological response of melanoma patients receiving melanoma cell vaccines. I. Autologous cultured melanoma cells. Int J Cancer. 1982 Oct 15;30(4):413–422. doi: 10.1002/ijc.2910300406. [DOI] [PubMed] [Google Scholar]
  7. Morgan D. A., Ruscetti F. W., Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science. 1976 Sep 10;193(4257):1007–1008. doi: 10.1126/science.181845. [DOI] [PubMed] [Google Scholar]
  8. Mukherji B., MacAlister T. J. Clonal analysis of cytotoxic T cell response against human melanoma. J Exp Med. 1983 Jul 1;158(1):240–245. doi: 10.1084/jem.158.1.240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Old L. J. Cancer immunology: the search for specificity--G. H. A. Clowes Memorial lecture. Cancer Res. 1981 Feb;41(2):361–375. [PubMed] [Google Scholar]
  10. PREHN R. T., MAIN J. M. Immunity to methylcholanthrene-induced sarcomas. J Natl Cancer Inst. 1957 Jun;18(6):769–778. [PubMed] [Google Scholar]
  11. Pfreundschuh M., Shiku H., Takahashi T., Ueda R., Ransohoff J., Oettgen H. F., Old L. J. Serological analysis of cell surface antigens of malignant human brain tumors. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5122–5126. doi: 10.1073/pnas.75.10.5122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Shiku H., Takahashi T., Oettgen H. F. Cell surface antigens of human malignant melanoma. II. Serological typing with immune adherence assays and definition of two new surface antigens. J Exp Med. 1976 Oct 1;144(4):873–881. doi: 10.1084/jem.144.4.873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ueda R., Shiku H., Pfreundschuh M., Takahashi T., Li L. T., Whitmore W. F., Oettgen H. F., Old L. J. Cell surface antigens of human renal cancer defined by autologous typing. J Exp Med. 1979 Sep 19;150(3):564–579. doi: 10.1084/jem.150.3.564. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES