Abstract
Even though mastocytoma P815 often undergoes a nearly complete rejection in syngeneic mice, the tumor cells almost always escape to form progressive tumors. We found that this was not due to the establishment of an immunosuppressed state because genetically marked P815 cells, that were injected in mice where tumor escape was occurring, were readily rejected. An analysis of escaping tumor cell populations with anti-P815 cytolytic T lymphocyte (CTL) clones showed the presence of stable resistant variants. Using antigen-loss variants found in escaping populations or selected in vitro with CTL clones, we were able to define four different tumor-associated antigenic specificities, each recognized by a specific CTL clone. One of these specificities was absent from all escaping tumor cells and another had been lost by some of them.
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Selected References
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- Berendt M. J., North R. J., Kirstein D. P. The immunological basis of endotoxin-induced tumor regression. Requirement for a pre-existing state of concomitant anti-tumor immunity. J Exp Med. 1978 Dec 1;148(6):1560–1569. doi: 10.1084/jem.148.6.1560. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Biddison W. E., Palmer J. C. Development of tumor cell resistance to syngeneic cell-mediated cytotoxicity during growth of ascitic mastocytoma P815Y. Proc Natl Acad Sci U S A. 1977 Jan;74(1):329–333. doi: 10.1073/pnas.74.1.329. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boon T., Van Snick J., Van Pel A., Uyttenhove C., Marchand M. Immunogenic variants obtained by mutagenesis of mouse mastocytoma P815. II. T lymphocyte-mediated cytolysis. J Exp Med. 1980 Nov 1;152(5):1184–1193. doi: 10.1084/jem.152.5.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bosslet K., Schirrmacher V. Escape of metastasizing clonal tumor cell variants from tumor-specific cytolytic T lymphocytes. J Exp Med. 1981 Aug 1;154(2):557–562. doi: 10.1084/jem.154.2.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dye E. S., North R. J. T cell-mediated immunosuppression as an obstacle to adoptive immunotherapy of the P815 mastocytoma and its metastases. J Exp Med. 1981 Oct 1;154(4):1033–1042. doi: 10.1084/jem.154.4.1033. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Germain R. N., Dorf M. E., Benacerraf B. Inhibition of T-lymphocyte-mediated tumor-specific lysis by alloantisera directed against the H-2 serological specificities of the tumor. J Exp Med. 1975 Oct 1;142(4):1023–1028. doi: 10.1084/jem.142.4.1023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maryanski J. L., Marchand M., Uyttenhove C., Boon T. Immunogenic variants obtained by mutagenesis of mouse mastocytoma P815. VI. Occasional escape from host rejection due to antigen-loss secondary variants. Int J Cancer. 1983 Jan 15;31(1):119–123. doi: 10.1002/ijc.2910310119. [DOI] [PubMed] [Google Scholar]
- Maryanski J. L., Van Snick J., Cerottini J. C., Boon T. Immunogenic variants obtained by mutagenesis of mouse mastocytoma P815. III. Clonal analysis of the syngeneic cytolytic T lymphocyte response. Eur J Immunol. 1982 May;12(5):401–406. doi: 10.1002/eji.1830120508. [DOI] [PubMed] [Google Scholar]
- PREHN R. T., MAIN J. M. Immunity to methylcholanthrene-induced sarcomas. J Natl Cancer Inst. 1957 Jun;18(6):769–778. [PubMed] [Google Scholar]
- Ryser J. E., Cerottini J. C., Brunner K. T. Generation of cytolytic T lymphocytes in vitro. IX. induction of secondary CTL responses in primary long-term MLC by supernatants from secondary MLC. J Immunol. 1978 Feb;120(2):370–377. [PubMed] [Google Scholar]
- Takei F., Levy J. G., Kilburn D. G. Characterization of suppressor cells in mice bearing syngeneic mastocytoma. J Immunol. 1977 Feb;118(2):412–417. [PubMed] [Google Scholar]
- Takei F., Levy J. G., Kilburn D. G. In vitro induction of cytotoxicity against syngeneic mastocytoma and its suppression by spleen and thymus cells from tumor-bearing mice. J Immunol. 1976 Feb;116(2):288–293. [PubMed] [Google Scholar]
- Tilkin A. F., Schaaf-Lafontaine N., Van Acker A., Boccadoro M., Urbain J. Reduced tumor growth after low-dose irradiation or immunization against blastic suppressor T cells. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1809–1812. doi: 10.1073/pnas.78.3.1809. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Urban J. L., Burton R. C., Holland J. M., Kripke M. L., Schreiber H. Mechanisms of syngeneic tumor rejection. Susceptibility of host-selected progressor variants to various immunological effector cells. J Exp Med. 1982 Feb 1;155(2):557–573. doi: 10.1084/jem.155.2.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Uyttenhove C., Van Snick J., Boon T. Immunogenic variants obtained by mutagenesis of mouse mastocytoma P815. I. Rejection by syngeneic mice. J Exp Med. 1980 Nov 1;152(5):1175–1183. doi: 10.1084/jem.152.5.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van Snick J., Uyttenhove C., Van Pel A., Boon T. Stimulation of cytolytic T lymphocytes by azaguanine-resistant mouse tumor cells in selective HAT medium. J Immunol Methods. 1981;46(3):321–326. doi: 10.1016/0022-1759(81)90317-3. [DOI] [PubMed] [Google Scholar]
- Weinhold K. J., Goldstein L. T., Wheelock E. F. The tumor dormant state. Quantitation of L5178Y cells and host immune responses during the establishment and course of dormancy in syngeneic DBA/2 mice. J Exp Med. 1979 Mar 1;149(3):732–744. doi: 10.1084/jem.149.3.732. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weinhold K. J., Miller D. A., Wheelock E. F. The tumor dormant state. Comparison of L5178Y cells used to establish dormancy with those that emerge after its termination. J Exp Med. 1979 Mar 1;149(3):745–757. doi: 10.1084/jem.149.3.745. [DOI] [PMC free article] [PubMed] [Google Scholar]