CIS-DIAMMINEDICHLOROPLATINUM(II) AUGMENTS EXPRESSION OF TUMOR-ASSOCIATED ANTIGENS ON HUMAN GASTRIC-CANCER CELL-LINE KATO-3 AND INCREASES SUSCEPTIBILITY AND BINDING OF TUMOR-CELLS TO VARIOUS CYTOTOXIC EFFECTOR-CELLS

Previous studies have demonstrated the immunomodulatory effects of cis platin under certain conditions. The present study was designed to cla rify whether cisplatin modulates the expression of surface antigens, e specially human leukocyte antigen (HLA), on human tumor cell lines and /or augments the susceptibility and binding of tumor cells to cytotoxi c effector cells. A human gastric cancer cell line, KATO-3, was employ ed. The expression of HLA and other tumor-associated antigens was anal yzed by flow cytometry using FITC-conjugated monoclonal antibodies. Th e cytotoxicity of effector cells was determined by Cr-51 release assay . The expression of HLA class I antigen, beta(2)-microglobulin, leukoc yte function-associated antigen-1, and AC-81 adenocarcinoma-associated antigen on KATO-3 increased after exposure to cisplatin at 10 mu g/ml for 3-6 hr; augmentation of HLA class I subtypes -B2 and -B27 was par ticularly prominent. Furthermore, the susceptibility and binding of KA TO-3 to both lymphokine-activated killer cells and KATO-3-specific cyt otoxic T lymphocytes significantly increased after cisplatin treatment . Cisplatin may modulate the expression of tumor-associated antigens o n some human tumor cells. Tumor regression by cisplatin administration may depend on its direct cytotoxicity as well as on its modulating ef fects on the expression of tumor-associated antigens, subsequently lea ding to the activation of the immune surveillance system against the t umor. (C) 1996 Wiley-Liss, Inc.