The Expression of Adenosine A2B Receptor on Antigen-Presenting Cells Suppresses CD8+ T-cell Responses and Promotes Tumor Growth.

Siqi Chen, Imran Akdemir, Jie Fan, Joel Linden, Bin Zhang, Caglar Cekic

Cancer immunology research 2020 Aug

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Accumulating evidence suggests that inhibiting adenosine-generating ecto-enzymes (CD39 and CD73) and/or adenosine A2A or A2B receptors (R) stimulates antitumor immunity and limits tumor progression. Although activating A2ARs or A2BRs causes similar immunosuppressive and protumoral functions, few studies have investigated the distinct role of A2BR in cancer. Here, we showed that A2BR expression by hematopoietic cells was primarily responsible for promoting tumor growth. Deletion of A2BR profoundly enhanced anticancer T-cell immunity. Although T-cell A2BR plays an insignificant role for A2BR-mediated immunosuppression and tumor promotion, A2BR deficiency in tumor-bearing mice caused increased infiltration of myeloid and CD103+ dendritic cells, which was associated with more effective cross-priming of adoptively transferred tumor antigen-specific CD8+ T cells. A2BR deletion also intrinsically favored accumulation of myeloid and CD11bdim antigen-presenting cells (APC) in the tumor microenvironment. Both myeloid-specific or CD11c-specific conditional deletion of A2BR delayed primary tumor growth. Myeloid, but not CD11c-specific conditional, depletion delayed lung metastasis. Pharmacologic blockade of A2BR improved the antitumor effect of adoptive T-cell therapy. Overall, these results suggested that A2BR expression on myeloid cells and APCs indirectly suppressed CD8+ T-cell responses and promoted metastasis. These data provide a strong rationale to combine A2BR inhibition with T-cell-based immunotherapy for the treatment of tumor growth and metastasis. ©2020 American Association for Cancer Research.

Citation

Siqi Chen, Imran Akdemir, Jie Fan, Joel Linden, Bin Zhang, Caglar Cekic. The Expression of Adenosine A2B Receptor on Antigen-Presenting Cells Suppresses CD8+ T-cell Responses and Promotes Tumor Growth. Cancer immunology research. 2020 Aug;8(8):1064-1074