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 cisplatin under certain conditions. The present study was designed to clarify whether cisplatin modulates the expression of surface antigens, especially human leukocyte antigen (HLA), on human tumor cell lines and/or augments the susceptibility and binding of tumor cells to cytotoxic effector cells. A human gastric cancer cell line, KATO-3, was employed. The expression of HLA and other tumor-associated antigens was analyzed by flow cytometry using FITC-conjugated monoclonal antibodies. The cytotoxicity of effector cells was determined by 51Cr release assay. The expression of HLA class I antigen, beta2-microglobulin, leukocyte function-associated antigen-1, and AC-81 adenocarcinoma-associated antigen on KATO-3 increased after exposure to cisplatin at 10 micrograms/ml for 3-6 hr; augmentation of HLA class I subtypes -B2 and -B27 was particularly prominent. Furthermore, the susceptibility and binding of KATO-3 to both lymphokine-activated killer cells and KATO-3-specific cytotoxic T lymphocytes significantly increased after cisplatin treatment. Cisplatin may modulate the expression of tumor-associated antigens on some human tumor cells. Tumor regression by cisplatin administration may depend on its direct cytotoxicity as well as on its modulating effects on the expression of tumor-associated antigens, subsequently leading to the activation of the immune surveillance system against the tumor.
Hayashi
H
H
First Department of Surgery, Kyoto University, Faculty of Medicine, Japan.
Nio
Y
Y
Kawabata
K
K
Araya
S
S
Imamura
M
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000187:drug effects* / Q000276:immunology; D000954:Antigens, Surface / Q000187:drug effects / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002277:Carcinoma / Q000276:immunology*; D002945:Cisplatin / Q000494:pharmacology*; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry / Q000379:methods; D006680:HLA Antigens / Q000187:drug effects / Q000276:immunology; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed / Q000379:methods; D013268:Stimulation, Chemical; D013274:Stomach Neoplasms / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D000970:Antineoplastic Agents; D006680:HLA Antigens; D002945:Cisplatin