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Reversal by Peritoneal Adherent Cells of Tumor Cell Suppression of T Cell-Mediated Immunity

From the Laboratory of Cell Biology, National Cancer Institute, Bethesda, Maryland 20205

Abstract

Tumor cells and their cell/free products were found to be suppressive for the T cell-mediated cytotoxic response. This was shown by their ability to inhibit the standard mixed lymphocyte culture (MLC) reactions and the failure of these tumor cells to induce cytotoxic response in the allogeneic mixed lymphocyte tumor cell culture (MLTC) reactions. However, this immunosuppressive effect could be completely reversed by the addition of 1 to 10% of syngeneic peritoneal cells (PC) into the MLC or MLTC reactions. Addition of PC not only can reverse the immunosuppression of tumor cells in MLC, but also restores the cytotoxic response to these tumor cells in MLTC. Although PC were needed to restore the cytotoxic response, the cytotoxic effector cells recovered from these cultures were found to be entirely T cells. These PC were needed in the early induction phase of the cytotoxic response. The reversal of immunosuppression can only be obtained when PC were added at the onset of MLTC reactions. Addition of PC at a later time or were left in the effector phase of cytotoxic reactions gave no restoration of the cytotoxic response. In the FBL-3 tumor system, the PC that were responsible for the reversal of the immunosuppression were found to be radioresistant, adherent, Thy. 1-antigen negative, Ia-negative, and Ig-negative. They were also found to be predominantly nonphagocytes. Therefore, they were not typical macrophages. This nonphagocytic population of adherent PC may play a critical role in the regulation of T cell-mediated cytotoxic response to tumor cells.