Cellular Mechanisms of Immunodepression in Tumor-bearing Rats

Tumor-specific cellular immunity to tumor antigens was demonstrated in vitro by mixed lymphocyt tumor interaction (MLTI). Tumor antigens were extracted from 3-methylcholanthrene induced fibrosarcomas (KMT-17) with 3 M KCl. Spleen cells from rats immunized with KMT-17 tumor by ligationfree technique had a strong reactivity in MLTI and could neutrlize the tumor challenge (Winn test). The MLTI responses and tumor neutralization effects of tumor-immune spleen cells were abolished by treatment with anti-T serum and complement but not by nylon wool passage, indicating that the responsible cell type in MLTI and Winn assay was the T cell. Since this MLTI reaction had tumor specificity, tumor antigens extracted with 3M KCl appear to be tumor-specific antigens (TSA). Impairment of lymphoproliferative response to PHA and in MLC and MLTI was detected in the spleens of rats hearing KMT-17 tumors. The residual cells after depletion of macrophages from tumorbearer's spleen cells could respond to PHA and MLC but not to MLTI. When the spleen cells or thymus cells from tumor bearing rats were added to PHA, MLC and MLTI responses, spleen cells suppressed PHA, MLC and MLTI responses, whereas thymus cells suppressed MLTI responses but not to PHA. Evidence was presented for two distinct suppressor cell systems, one of which was the suppressor T cell system and the other of which was the suppressor macrophage system. Suppressor T cells were demonstrated in both the tumor-bearer's thymus cells and spleen cells, while suppressor macrophages were demonstrated in the tumor-hearer's spleen cells. T cells suppressed only MLTI responses while macrophages suppressed not only MLTI but also PHA and MLC responses. These suppressor cells, although suppressing lymphoblastogenic responses, could not impair the activity of tumor-immune spleen cells to neutralize tumor growth. These results suggest that two different suppressor mechanisms are involved in immunodepression observed in tumor-bearing hosts, which may have some relation to the so-called ‘escape’ mechanism in tumor immunity