T cell-derived IL-10 promotes lung cancer growth by suppressing both T cell and APC function

We have found previously that human lung cancers potently induce T lymphocy te IL-10 production in vitro. To assess the impact of enhanced T cell-deriv ed IL-10 on antitumor immunity in vivo, we utilized transgenic mice express ing IL-10 under the control of the IL-2 promoter. We have shown previously that Lewis lung carcinoma cells (3LL) have more aggressive growth potential in IL-10 transgenic mice compared with control littermates. In this study, we show that transfer of T cells from IL-10 transgenic mice to control lit termates transferred the IL-10 immunosuppressive effect and led to enhanced 3LL tumor growth. In addition to changes in T cell-mediated immunity, prof essional APC from IL-10 transgenic mice were found to have significantly su ppressed capacity to induce MHC alloreactivity, CTL responses, and IL-12 pr oduction. Tumor Ag-pulsed dendritic cells from IL-10 transgenic mice also f ailed to generate antitumor reactivity. These results suggest that increase d levels of T cell-derived IL-10 severely impair antitumor immunity in vivo , due to defects in both T cell and APC function.