Induction of tumor-specific antitumor immunity after chemotherapy with cisplatin in mice bearing MOPC-104E plasmacytoma by modulation of MHC expression on tumor surface.

Abstract

Chemotherapy sometimes results in induction of specific antitumor immunity. We investigated the mechanisms responsible for the induction of antitumor immunity in mice bearing MOPC-104E plasmacytoma after chemotherapy with cisplatin (CDDP), especially the effects of CDDP on the expression of MHC on the tumor surface. BALB/c mice were subcutaneously (s.c.) inoculated with MOPC-104E cells on day 0, then intravenously (i.v.) treated with CDDP at 3.6 mg/kg on day 7. The tumors disappeared completely on day 35 and the mice rejected a second challenge with MOPC-104E, but did not reject syngeneic Meth-A fibrosarcoma. The tumors did not regress, however, when MOPC-104E was s.c. transplanted in nude mice, or when anti-T-cell monoclonal antibodies were i.v. injected into BALB/c mice before CDDP treatment on day 6. To determine which of the mice or tumor were affected by CDDP, BALB/c mice were inoculated with CDDP-treated (12.5 micrograms/ml for 3 hours in vitro) MOPC-104E cells on day 0, 7 and 14. The potential to reject MOPC-104E was lower in mice immunized with ethanol-treated MOPC-104E cells than in those immunized with CDDP-treated cells. CDDP-treated or -untreated MOPC-104E cells ultrasonicated and fractionated into soluble and insoluble fractions by centrifuging, also induced antitumor immunity. Flow cytometry demonstrated that the expression of MHC-class-I antigens H-2Dd and H-2Kd was enhanced after CDDP-treatment, but that of class-II antigens I-Ad and I-Ed was not, suggesting that CDDP induced tumor-specific antitumor immunity by enhancing the expression of MHC-class-I antigens.