Suppressive effects of visceral tumor on the generation of antitumor T cells for adoptive immunotherapy

Abstract

Antitumor reactive cells can be generated from lymphoid organs of mice bearing subcutaneous (SC), but not liver or lung, tumors by in vitro sensitization with irradiated tumor and interleukin 2. To examine whether visceral tumors mediated tumor-induced suppression, in vitro sensitization cells were generated from mice bearing SC tumors with and without concomitant liver or lung tumors. Antitumor efficacy of these cells was assessed in adoptive immunotherapy experiments. The presence of visceral tumors suppressed the ability to generate therapeutic in vitro sensitization cells from mice with SC tumors. By establishing visceral tumors at different intervals in relationship to SC tumor inoculation, we found that visceral tumor appeared to suppress directly the development of a host immune response to SC tumor, rather than inhibit function of established immune cells. Our model affords a means to study mechanisms of tumor-induced immunosuppression.