CD73 is a cell surface
enzyme that suppresses T cell-mediated immune responses by producing extracellular
adenosine. Growing evidence suggests that targeting CD73 in
cancer may be useful for an effective therapeutic outcome. In this study, we demonstrate that administration of a specific CD73 inhibitor,
adenosine 5'-(α,β-methylene)diphosphate (
APCP), to
melanoma-bearing mice induced a significant
tumor regression by promoting the release of Th1- and Th17-associated
cytokines in the tumor microenvironment. CD8+ T cells were increased in
melanoma tissue of
APCP-treated mice. Accordingly, in nude mice
APCP failed to reduce
tumor growth. Importantly, we observed that after
APCP administration, the presence of B cells in the
melanoma tissue was greater than that observed in control mice. This was associated with production of
IgG2b within the
melanoma. Depletion of CD20+ B cells partially blocked the anti-
tumor effect of
APCP and significantly reduced the production of
IgG2b induced by
APCP, implying a critical role for B cells in the anti-
tumor activity of
APCP. Our results also suggest that
APCP could influence B cell activity to produce
IgG through
IL-17A, which significantly increased in the
tumor tissue of
APCP-treated mice. In support of this, we found that in
melanoma-bearing mice receiving anti-IL-17A mAb, the anti-
tumor effect of
APCP was ablated. This correlated with a reduced capacity of
APCP-treated mice to mount an effective immune response against
melanoma, as neutralization of this
cytokine significantly affected both the CD8+ T cell- and B cell-mediated responses. In conclusion, we demonstrate that both T cells and B cells play a pivotal role in the
APCP-induced anti-
tumor immune response.