IMMUNOHISTOCHEMICAL FEATURES OF HLA-DR ANTIGEN EXPRESSION AND LYMPHOID INFILTRATES IN GASTRIC-CARCINOMA AFTER LOW-DOSE INTERLEUKIN-2 AND MITOMYCIN-C

We immunohistochemically evaluated lymphoid cell infiltration and HLA- DR antigen expression in gastric tumor tissue obtained from advanced g astric cancer patients 1 day after the completion of the treatment wit h mitomycin C (MMC) 12 mg/m(2) i.v. on day 1 and recombinant interleuk in-2 (IL-2) i.v. every 12 h from day 4 through day 8. Then the results were compared with those in 11 patients pretreated with MMC alone, 5 treated with IL-2 alone, and 24 untreated patients. Widespread lymphoi d infiltration was observed in 17% of untreated tumors, 27% of MMC-pre treated tumors, and 40% of tumors treated with IL-2 alone. However, 71 % of carcinomas pretreated with MMC plus IL-2 exhibited widespread inf iltration. The frequency of cases with high-grade infiltration of CD4( +) cells was significantly higher in either group of patients treated with MMC alone or MMC plus IL-2. Because the CD8(+) cell infiltration was not significantly altered, the ratio of CD4(+) to CD8(+) cells est imated as being > 1 was more frequently noted in patients given MMC al one or MMC plus IL-2, as compared with untreated control. Furthermore, 86% of tumors pretreated with MMC plus IL-2 exhibited positive HLA-DR antigen expression, whereas 29% of untreated carcinomas did so. MMC o r IL-2 alone did not significantly increase HLA-DR expression. These r esults indicate that the combination of low-dose of IL-2 with MMC enha nces the intensity of lymphoid cell infiltration in tumors, with the p redominance of CD4(+) cells, and HLA-DR antigen expression on tumor ce lls in patients with advanced gastric carcinoma.