The expression of adenosine A2B receptor on antigen-presenting Cells suppresses CD8+ T-cell responses and promotes tumor growth

buir.contributor.authorAkdemir, İmran
buir.contributor.authorÇekiç, Çağlar
dc.citation.epage1074en_US
dc.citation.issueNumber8en_US
dc.citation.spage1064en_US
dc.citation.volumeNumber8en_US
dc.contributor.authorChen, S.
dc.contributor.authorAkdemir, İmran
dc.contributor.authorFan, J.
dc.contributor.authorLinden, J.
dc.contributor.authorZhang, B.
dc.contributor.authorÇekiç, Çağlar
dc.date.accessioned2021-02-25T11:49:32Z
dc.date.available2021-02-25T11:49:32Z
dc.date.issued2020-05
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractAccumulating 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.en_US
dc.identifier.doi10.1158/2326-6066.CIR-19-0833en_US
dc.identifier.issn2326-6074
dc.identifier.urihttp://hdl.handle.net/11693/75590
dc.language.isoEnglishen_US
dc.publisherNLM (Medline)en_US
dc.relation.isversionofhttps://dx.doi.org/10.1158/2326-6066.CIR-19-0833en_US
dc.source.titleCancer immunology researchen_US
dc.titleThe expression of adenosine A2B receptor on antigen-presenting Cells suppresses CD8+ T-cell responses and promotes tumor growthen_US
dc.typeArticleen_US

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