Suppressive effects of visceral tumor on the generation of antitumor T cells for adoptive immunotherapy
V. K. Sondak, P. D. Wagner, S. Shu and A. E. Chang
Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109-0331.
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.
