Deletion of adenosine A2A receptors on CD8 T cells enhances their accumulation in tumors and tumor-draining lymph nodes, as well as their ability to control tumor outgrowth (40.6)

Abstract

Abstract Previous work has demonstrated that ablation of adenosine A2A receptor (A2AR) expression in tumor-bearing mice enhances tumor control. However, it is not yet clear what cells and functions are influenced by A2AR signaling. Here we show that the ability of adoptively transferred OT-I CD8 T cells to control ovalbumin expressing B16 melanomas in A2aR+/+ recipients is enhanced if the A2AR gene is ablated in the OT-I cells. This demonstrates directly that the ability of CD8 T cells to control tumors is influenced by adenosine. To further understand the functions of CD8 T cells influenced by A2AR deletion, we examined the activation, proliferation, and survival of A2AR+/+ and A2AR-/- OT-I cells in tumors and tumor-draining lymph nodes (TDLN) after co-transfer. While activation and proliferation of both populations in TDLN was comparable, the accumulation of A2AR-/- cells in both TDLN and tumor was enhanced relative to A2AR+/+ cells. Preliminary data suggest that this is due to enhanced survival of A2AR-/- CD8 T cells in TDLN. This enhanced accumulation does not occur in the lymph nodes of mice immunized with bone marrow derived dendritic cells or Vaccinia virus, suggesting that it reflects alterations in the level of adenosine specifically in TDLN. We theorize that enhanced accumulation of A2AR-/- CD8 T cells is at least partially responsible for their increased ability to control tumors. Support: NIH R01 CA78400, F31 CA130117