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 gastric cancer patients 1 day after the completion of the treatment with mitomycin C (MMC) 12 mg/m2 i.v. on day 1 and recombinant interleukin-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 lymphoid infiltration was observed in 17% of untreated tumors, 27% of MMC-pretreated tumors, and 40% of tumors treated with IL-2 alone. However, 71% of carcinomas pretreated with MMC plus IL-2 exhibited widespread infiltration. 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 estimated as being > 1 was more frequently noted in patients given MMC alone 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 or IL-2 alone did not significantly increase HLA-DR expression. These results indicate that the combination of low-dose of IL-2 with MMC enhances the intensity of lymphoid cell infiltration in tumors, with the predominance of CD4+ cells, and HLA-DR antigen expression on tumor cells in patients with advanced gastric carcinoma.
Inoue
H
H
Department of Surgery, Kyushu University, Beppu, Japan.
Arinaga
S
S
Adachi
M
M
Asoh
T
T
Ueo
H
H
Akiyoshi
T
T
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000737:chemistry* / Q000188:drug therapy / Q000276:immunology; D004334:Drug Administration Schedule; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis / Q000187:drug effects*; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use; D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry* / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000276:immunology
D006684:HLA-DR Antigens; D007376:Interleukin-2; D016685:Mitomycin