Opposing effects of myeloid vs. lymphoid deletion of adenosine A2A receptors on anti-tumor immune responses (P2007)

Abstract

Abstract Extracellular adenosine is generated as part of immune escape programming orchestrated by tumor cells and regulatory cells. Adenosine A2A receptors (A2AR) on innate and adaptive immune cells are high affinity targets for adenosine-mediated immune suppression. In this study we demonstrate that myeloid-deletion of adenosine A2A receptor gene (adora2a) strongly inhibit tumor growth and metastasis. This was associated with increased APC function of macrophages and increased the numbers and activation of cytotoxic lymphocytes. Surprisingly, lymphoid deletion of adora2a markedly increased tumor growth and decreased the numbers of effector/memory T cells in the tumor. Mechanistic studies revealed that adora2a deletion in T cells severely impacts generation of the long/lived memory/effector T cell population within the tumor consistent with recent studies indicating that A2AR activation reduces activation-induced cell death. The results of this study have important implications for the development cell-based therapies targeting adenosine receptors.