Regulatory T cells (Treg) play a role in suppression of immune response, including anti-
tumor immunity. We have recently reported that treatment of naïve CD4 T cells with
adenosine A(2B) receptor antagonist
PSB603 under Treg-skewing conditions inhibits expression of Foxp3, a marker of differentiation to Treg, without blocking
IL-2 production or CD25 expression, which are activation markers, in CD4 T cells. We hypothesized that
PSB603 suppresses
cancer growth and
metastasis by inhibiting induction of Treg, thereby facilitating anti-
tumor immunity. In this study, we first examined the effect of
PSB603 on
tumor growth in
B16 melanoma-bearing C57BL/6 mice. Administration of
PSB603 significantly suppressed the increase of
tumor volume as well as the increase of Treg population in these mice. The populations of CD4 and CD8 T cells were higher and splenic lymphocyte-mediated cytotoxicity towards
B16 melanoma was significantly increased in PSB603-treated mice. We confirmed that
PSB603 did not reduce the viability of
B16 melanoma cells in vitro. Moreover, we also examined the effect of
PSB603 on
tumor metastasis in pulmonary
metastasis model mice intravenously injected with
B16 melanoma cells. The
metastasis was also suppressed in PSB603-treated mice, in which the population of Treg was significantly lower. Overall, our results suggest that A(2B) receptor antagonist
PSB603 enhances anti-
tumor immunity by inhibiting differentiation to Treg, resulting in a delay of
tumor growth and a suppression of
metastasis.