Abstract
The concentrated supernatants of nine human melanoma cell line cultures were analyzed for the presence of factors that inhibitin vitro immunological reactions. All cell lines secreted a factor that inhibited LPS-induced proliferation of murine B cells; eight cell lines released a factor that inhibited PHA-induced proliferation of murine T cells; all of the three cell lines investigated secreted a factor that inhibited the allogeneic stimulation of BALB/c spleen cells by mitomycin-C-treated C57BL spleen cells. Further analysis of the M21 cell supernatant indicated that its continuous presence was required for the inhibition of the PHA but not of the LPS response suggesting a different mechanism of action. High levels of PHA, but not of LPS, could overcome the inhibitory effect of M21 supernatants. Fractionation of M21 supernatants by sucrose gradient centrifugation, DEAE chromatography and gel filtration suggested that the anti-PHA and the anti-LPS activities were due to different factors. These factors differed from a serine proteinase inhibitor that is also released by M21 cells. Since these inhibitory factors may have a role in protecting a melanoma tumor from attack by the immune system of the host, their consideration may be helpful in designing protocols for therapy which include methods to boost the antitumor responses of the host.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Nelson, D S, Nelson M: Evasion of host defenses by tumors.Immunol Cell Biol 65, 287–304 (1987).
Roth J A, Osborne B A, Ames R S: Immunoregulatory factors derived from human tumors II. Partial purification and further immunobiochemical characterization of a human sarcoma-derived immunosup-pressive factor expressing HLA-OR and Immunoglobulin related determinant.J Immunol 130, 303–308 (1983).
Putnam J B, Roth J A: Identification and characterization of a tumor derived immunosuppressive gly-coprotein from murine melanoma K-1735.Cancer Immunol Immunother 19, 90–100 (1985).
Hoagland J G, Scoggin S, Giavazzi R, Campbell D, Kanellopoulos K, Jessup J M: Tumor derived suppressor factors (TDSFs) in normal and neoplastic colon and rectum.Surg Res 40, 467–474 (1986).
Cornelius J C, Normal S J: Isolation of a low M.W. inhibitor of lymphocyte proliferation from tumorous ascites.J Immunol 141, 2175–2180 (1988).
Whitehead J S, Kim Y S: An inhibitor of lymphocyte proliferation produced by a human colonic adenocar- cinoma cell line in culture.Cancer Res 40, 29–35 (1980).
Najmabadi F, Giacomoni D, Dray S: Serine pro-teinase inhibitors produced by human melanoma cell lines.Tumor Biol 11, 39–50 (1990).
Muller-Eberhard H J: The membrane attack complex of complement.Ann Rev Immunol 4, 503–528 (1986).
Pasternack M S, Verret C R, Liu M H, Eisen H N: Serine esterases in cytolytic T lymphocytes.Nature 322, 740–743 (1986).
Kaplan J C, Bona C: Proteases as mitogens.Exp Cell Res 88, 388–396 (1974).
Bromke B J, Kueppers F: The major urinary protease inhibitor: Simplified purification and characterization.Biochem Med 27, 56–67 (1982).
Werkmeister J, Zbroja R, McCarthy W, Hersey P: Detection of an inhibitor of cell division in cultures of tumor cells with immunosuppressive activityin vitro.Clin exp Immunol 40, 168–177 (1980).
Cordiali-Fei P, Mottolese M, Tecce R, Natali P, Ferrone S: Accessory cell function of human melanoma cells in mitogen-induced T-cell proliferation.Cell Immunol 116, 149–162 (1988).
Ye Q W, Mokyr M B, Pyle J M, Dray S: Suppression of antitumor immunity by macrophages bearing a large MOPC-315 tumor.Cancer Immunol Immunother 16, 162–169 (1984).
Nahas F, Ophir R, Ben-Efraim S: Effect of melphalan administration on the activity of natural killer and natural cytotoxic spleen cells of normal and tumor-bearing mice.Immunology Lett 10, 333–337 (1985).
Shoval S, Ophir R, Ben-Efraim S: Deficiency in immunocompetence of mice cured from large MOPC- 315 plasmacytoma by melphalan therapy.Cancer Immunol Immunother 29, 279–287 (1989).
Wise J A, Mokyr M B, Dray S: Effect of low dose cyclophosphamide therapy on specific and nonspecific T cell-dependent responses of spleen cells from mice bearing large MOPC-315 plasmacytomas.Cancer Immunol Immunother 27, 191–197 (1988).
Author information
Authors and Affiliations
Additional information
Supported by United States Public Health System Grant RO1-CA-44323 from the National Cancer Institute, NIH, Bethesda, MD.
Rights and permissions
About this article
Cite this article
Giacomoni, D., Ben-Efraim, S., Najmabadi, F. et al. Inhibitors of lymphocyte activation secreted by human melanoma cell lines. Med. Oncol. & Tumor Pharmacother. 7, 273–280 (1990). https://doi.org/10.1007/BF02987106
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02987106