Cell‐intrinsic adenosine A2A receptor signaling is required for T cell homeostasis and tumor surveillance

Abstract

Adenosine A2A receptors (A2ARs) are highly expressed in certain neuronal and immune cells and regulate locomotor activity, sleep, and immune functions. Thus, A2ARs are promising pharmacological targets in a wide range of conditions such as sleep disorders, inflammatory disorders and cancer. Although it is known that stimulation of A2ARs on T cells inhibits their activation, global deletion of A2ARs does not affect the growth of weakly immunogenic tumors. To study the role of A2ARs on T cells we generated a mouse line with T cell‐specific A2AR deletion. Here, we report that A2AR signaling is required to maintain normal numbers of peripheral naïve CD4 and CD8 T cells. T cell‐specific A2AR deletion does not affect thymic T cell differentiation but inhibits naïve T cell survival in response to interleukin‐7 ex vivo. In mice injected with syngeneic B16F10 melanoma cells, T cell specific A2AR deletion decreases T cell numbers in the periphery and in the tumor, reduces the proportion of tumor infiltrating T cells with an activated/memory phenotype, and markedly accelerates tumor growth. The results indicate that A2AR signaling is required for T cell homeostasis and control of tumor growth.