Abstract
Peripheral blood lymphocytes (PBL) of melanoma patients were sensitized in vitro with lymphocytes of a single donor or with a pool of lymphocytes of 5–20 different donors. After 6–7 days, the cytotoxic activity of the sensitized PBL was tested against cultured autologous tumor cells and lymphocytes in a 51Cr-release assay. Tumor lysis was observed in 13 of 16 cases in which patients' PBL (Pt-PBL) were stimulated by a pool of allogeneic lymphocytes and in five out of seven cases when single sensitization was performed. In no case was lysis of autologous normal lymphocytes or blasts seen. Cultivation of Pt-PBL with irradiated autologous tumor cells never led to the induction of lymphocytes cytotoxic to melanoma cells. Lysability by pool-activated autologous Pt-PBL of fresh cryopreserved tumor cells was compared to that of short-term cultured tumor cells, and no significant differences were observed. Cold-target inhibition experiments indicated that the cytotoxicity of Pt-PBL was tumor-restricted since only autologous melanoma cells but not lymphocytes were able to inhibit the reaction. These results indicate that activation of Pt-PBL is necessary in order to elicit or amplify their antitumor activity.
Keywords: Melanoma, Melanoma Cell, Peripheral Blood Lymphocyte, Melanoma Patient, Human Melanoma Cell
References
- 1.Bach FH, Leshem B, Kuperman OJ, Bunzendhal H, Alter BJ, Zarling JM. Allosensitization to obtain anti-tumor immunity. In: Fefer A, Goldstein AM, editors. The Potential Role of T Cells Subpopulations in Cancer Therapy. New York: Raven Press; 1982. [Google Scholar]
- 2.Du Pont G, Alexander M, Zehngebot L, Mitchell K, Herlyn M. Primary melanoma induces HLA-DR dependent autologous T-cell proliferation. Proc Am Ass Cancer Res. 1982;23:1076. [Google Scholar]
- 3.Hersey P, Bindon C, Edwards A, Murray E, Phillips G, McCarthy WH. Induction of cytotoxic activity in human lymphocytes against autologous and allogeneic melanoma cells in vitro by culture with interleukin 2. Int J Cancer. 1981;28:695. doi: 10.1002/ijc.2910280607. [DOI] [PubMed] [Google Scholar]
- 4.Kedar E, Herberman RB. Induction of NK-like anti-tumor reactivity in vitro and in vivo by IL-2. In: Herberman RB, editor. Natural Cell-Mediated Immunity, vol 2. New York: Academic Press; 1982. p. 859. [Google Scholar]
- 5.Landazuri OM, Herberman RB. Specificity of cellular immune reactivity to virus induced tumors. Nature. 1972;238:18. doi: 10.1038/newbio238018a0. [DOI] [PubMed] [Google Scholar]
- 6.Lotze MT, Grimm EA, Mazumder A, Strausser JL, Rosenberg SA. Lysis of fresh and cultured autologous tumor by human lymphocytes cultured in T-cell growth factor. Cancer Res. 1981;41:4420. [PubMed] [Google Scholar]
- 7.Mazumder A, Grimm EA, Zhang HZ, Rosenberg SA. Lysis of fresh human solid tumors by autologous lymphocytes activated in vitro with lectins. Cancer Res. 1982;42:913. [PubMed] [Google Scholar]
- 8.Moore M, Vose BM. Extravascular natural cytotoxicity in man: anti-K-562 activity of lymph-node and tumor infiltrating lymphocytes. Int J Cancer. 1981;27:265. doi: 10.1002/ijc.2910270303. [DOI] [PubMed] [Google Scholar]
- 9.Moretta L, Mingari MC, Sekaly PR, Moretta A, Chapuis B, Cerottini JC. Surface markers of cloned human T cells with various cytolytic activities. J Exp Med. 1981;154:569. doi: 10.1084/jem.154.2.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Paciucci PA, MacPhail S, Zarling JM, Bach FH. Lysis of syngeneic solid tumor cells by alloantigen stimulated mouse T and non-T cells. J Immunol. 1980;124:370. [PubMed] [Google Scholar]
- 11.Parmiani G, Carbone G, Invernizzi G, Pierotti MA, Sensi ML, Rogers MJ, Appella E. Alien histocompatibility antigens on tumor cells. Immunogenetics. 1979;9:1. [Google Scholar]
- 12.Parmiani G, Sensi ML, Carbone G, Colombo MP, Pierotti MA, Ballinari D, Hilgers J, Hilkens J. Cross-reactions between tumor cells and allogeneic normal tissues. Inhibition of a syngeneic lymphoma outgrowth in H-2 and non-H-2 alloimmune BALB/c mice. Int J Cancer. 1982;29:323. doi: 10.1002/ijc.2910290316. [DOI] [PubMed] [Google Scholar]
- 13.Sensi ML, Carbone G, Parmiani G. Original H-2d and alien H-2k-like antigens of a BALB/c fibrosarcoma as defined by in vitro and in vivo studies of cell-mediated immunity. Eur J Immunol. 1980;10:671. doi: 10.1002/eji.1830100904. [DOI] [PubMed] [Google Scholar]
- 14.Sensi ML, Parenza M, Parmiani G (1982) Alloreactivity and tumor antigens. Generation of syngeneic anti-lymphoma killer lymphocytes by alloimmunization with normal cells. J Natl Cancer Inst (in press) [PubMed]
- 15.Strausser JL, Mazumder A, Grimm EA, Lotze MT, Rosenberg SA. Lysis of human solid tumors by autologous cells sensitized in vitro to alloantigens. J Immunol. 1981;127:266. [PubMed] [Google Scholar]
- 16.Vanky F, Vose BM, Fopp M, Klein E. Human tumor-lymphocyte interaction in vitro. VI. Specificity of primary and secondary autologous lymphocyte-mediated cytotoxicity. J Natl Cancer Inst. 1979;62:1407. [PubMed] [Google Scholar]
- 17.Vanky F, Gorsky T, Gorsky Y, Masucci MG, Klein E. Lysis of tumor biopsy cells by autologous T lymphocytes activated in mixed cultures and propagated with T cell growth factor. J Exp Med. 1982;155:83. doi: 10.1084/jem.155.1.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Vose BM. Specific T-cell-mediated killing of autologous lung tumor cells. Cell Immunol. 1980;55:12. doi: 10.1016/0008-8749(80)90132-x. [DOI] [PubMed] [Google Scholar]
- 19.Vose BM, Bonnard GO. Human tumor antigens defined by cytotoxicity and proliferative responses of cultured lymphoid cells. Nature. 1982;296:359. doi: 10.1038/296359a0. [DOI] [PubMed] [Google Scholar]
- 20.Vose BM, Vanky F, Klein E. Lymphocyte cytotoxicity against autologous tumor biopsy cells in humans. Int J Cancer. 1977;20:512. doi: 10.1002/ijc.2910200407. [DOI] [PubMed] [Google Scholar]
- 21.Woodward JG, Fernandez PA, Daynes RA. Cell-mediated immune response to syngeneic UV-induced tumors. III. Requirement for an Ia+ macrophage in the in vitro differentiation of cytotoxic T lymphocytes. J Immunol. 1979;122:1196. [PubMed] [Google Scholar]
- 22.Zarling JM, Kung PC. Distinction between human cytotoxic T lymphocytes and NK cells by monoclonal antibodies. Nature. 1980;288:394. doi: 10.1038/288394a0. [DOI] [PubMed] [Google Scholar]
- 23.Zarling JM, Robins HI, Raich PC, Bach FH, Bach ML. Generation of cytotoxic T lymphocytes to autologous human leukemia cells by sensitization to pooled allogeneic normal cells. Nature. 1978;274:269. doi: 10.1038/274269a0. [DOI] [PubMed] [Google Scholar]