AUGMENTATION OF SPLENIC ANTITUMOR IMMUNITY BY LOCAL IMMUNOTHERAPY IN GASTRIC-CANCER PATIENTS

We previously reported that the antitumor effect of OK-432, a streptoc occal preparation, was markedly augmented when this agent was injected into tumors together with fibrinogen. In order to elucidate the effec t of this treatment on the spleen, we assessed splenic function in gas tric cancer patients receiving preoperative local immunotherapy with O K-432 and fibrinogen. Immunohistochemical studies of the spleen at 7 d ays after intratumoral injection therapy revealed numerous macrophages phagocytizing OK-432 in the splenic sinuses. Phenotypic analysis of s plenocytes by flow cytometry revealed an increase in the CD4/CD8 ratio and in the expression of HLA-DR, CD25, and Leu M3 by splenic T cells of the patients treated with OK-432 plus fibrinogen when compared to p atients treated with OK-432 alone or untreated patients. Splenic T cel ls from patients treated with OK-432 plus fibrinogen showed significan tly higher cytotoxicity against Daudi and K562 cells than T cells from control patients (p<0.05), and culture of these splenic T cells with recombinant IL-2 induced the expansion of lymphokine-activated killer cells. These results demonstrate that local immunotherapy with a mixtu re of OK-432 and fibrinogen effectively augmented splenic antitumor im munity in gastric cancer patients.