Tolerance induction in tumor-specific effector T cells by presensitization with tumor antigens via the intragastric route.

Abstract

The present study deals with the influence of presensitization with tumor antigens via the intragastric route on the development of syngeneic tumor-specific immunity. Tumor-specific T cell-mediated immunity could be induced in C3H/He mice by intradermal inoculation of syngeneic X5563 tumor cells, followed by the surgical resection of the tumor 7 days later (immunization procedure). However, when the mice were presensitized intragastrically (ig) with 10(8) X-irradiated (10,000 R) tumor cells for four consecutive days, these mice failed to show in vivo protective immunity even after the above immunization procedure. Winn assays performed with spleen cells from mice presensitized ig with X5563 tumor cells revealed that ig-induced suppression was specific for the tumor antigen used for the presensitization, and that suppressor cell activity was not detected in the induction or implementation of in vivo tumor-specific effector cell activity. It was also demonstrated that such unresponsiveness was accompanied by failure to develop delayed-type hypersensitivity and cytotoxic T cell responses to X5563 tumor antigens. These results are discussed in the light of the effect of presensitization with tumor antigens via inappropriate routes on the subsequent induction of in vivo tumor-specific immunity and in relation to the tumor escape mechanism which could occur in gastrointestinal cancers.