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Modification of Host Antitumor Defense Mechanisms in Mice by Progressively Growing Tumor¹

Grace Cancer Drug Center, Roswell Park Memorial Institute, New York State Department of Health, Buffalo, New York 14263

The EL4 lymphoma in C57BL/6 mice was used as a model to examine the effect of progressive tumor growth on a variety of cell mediated cytolytic effector functions which have been shown in other systems to have antitumor potential. The functions examined were those of cytotlytic T-lymphocyte, lymphokine activated killer cells, natural killer cells, and tumoricidal macrophage (MO). The kinetics of each function displayed a unique pattern as a consequence of tumor growth, but all were inhibited in animals bearing large tumors (late tumor bearers). In cell mixing experiments it was shown that spleen cells from individual late tumor bearers were suppressive for cytotoxic T-lymphocytes, lymphokine activated killer cells, and splenic MO but not peritoneal MO or splenic natural killer cells. The suppression was nonspecific and was mediated primarily by nonadherent cells and/or their soluble products. Suppression appeared to be mediated, in part, by tumor cells in the spleen since the degree of suppressor activity associated with a particular spleen cell preparation correlated with the number of tumor cells present. Furthermore, the direct addition of viable ascites EL4 cells to response cultures or assays had similar suppressive effects as late TBM spleen cells, i.e., inhibited cytotoxic T-lymphocytes, lymphokine activated killer cells, and splenic MO but had no effect on natural killer cells or peritoneal MO. The mechanism of suppression by ascited EL4 was not determined but it was mediated by viable cells only and not due to contaminating viruses or other microorganisms.

¹ Supported in part by USPHS Grants CA-15142, CA-13038, CA-24538, and CA-09072 awarded by the National Cancer Institute, Department of Health and Human Services.

² Present address: Research and Development, Gibco Laboratories, Grand Island, NY 14072.

³ To whom requests for reprints should be addressed.

Received 7/18/88. Revised 12/27/88. Revised 4/18/89. Accepted 5/ 3/89.

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