ENHANCEMENT OF TUMOR-CELL SUSCEPTIBILITY TO TUMOR-INFILTRATING LYMPHOCYTES BY CISPLATIN

Some means of enhancing the susceptibility of tumor cells to tumor-inf iltrating lymphocytes (TIL) are required in adoptive immunotherapy. Th is study was designed to investigate whether or not tumor cell lysis b y TIL was enhanced by treatment of the tumor cells with cisplatin, and also to clarify the mechanism of cisplatin's action on tumor cells. A utologous tumor cells and established cancer cell lines, including KAT O-III and MKN-28, were used. Cytotoxic activities of TIL, the surface antigens of tumor cells, conjugation of TIL and tumor cells, and the p roduction of TNF alpha from TIL were analyzed. Tumor cells treated wit h 2 mu g/ml cisplatin for 12 h in vitro were more susceptible to bulk- cultured TIL and TIL clones. The surface antigens of tumor cells were not altered by the treatment with cisplatin. Cisplatin-treated tumor c ells showed a higher binding ratio to TIL than did non-treated tumor c ells. The anti-(tumor necrosis factor) (anti-TNF) or anti-TNF receptor antibody blocked the enhancement of cytotoxic activity by cisplatin. Thus, it was clarified that cisplatin enhanced the susceptibility of t umor cells to bulk-cultured TIL and TIL clones. Furthermore, the enhan cement of cytotoxic activity by TIL in cisplatin-treated tumor cells w as caused by a higher binding ratio to TIL and higher susceptibility t o the TNF produced by TIL.