Optimal population of FoxP3 + t cells in tumors requires an antigen priming-dependent trafficking receptor switch

Abstract

FoxP3 + T cells populate tumors and regulate anti-tumor immunity. The requirement for optimal population of FoxP3 + regulatory T cells in tumors remains unclear. We investigated the migration requirement and stability of tumor-associated FoxP3 + T cells. We found that only memory, but not naïve, FoxP3 + T cells are highly enriched in tumors. Almost all of the tumor-infiltrating FoxP3 + T cells express Helios, an antigen associated either with thymus-generated FoxP3 + T cells or activated T cells in the periphery. The tumor-infiltrating FoxP3 + T cells largely lack CD62L and CCR7, two trafficking receptors required for T cell migration into secondary lymphoid tissues. Instead, the tumor infiltrating FoxP3 + T cells highly express memory/tumor-associated CCR8 and CXCR4. Antigen priming is required for induction of this trafficking receptor phenotype in FoxP3 + T cells and only antigen primed, but not antigen-inexperienced naive, FoxP3 + T cells can efficiently migrate into tumors. While the migration of FoxP3 + T cells into tumors was a readily detectable event, generation of induced FoxP3 + T cells within tumors was unexpectedly inefficient. Genetic marking of current and ex-FoxP3 + T cells revealed that tumor-infiltrating FoxP3 + T cells are highly stable and do not readily convert back to FoxP3 - T cells. Taken together, our results indicate that population of tumors with thymus-generated FoxP3 + T cells requires an antigen priming-dependent trafficking receptor switch in lymphoid tissues. © 2012 Wang et al.