ArticleFrontiers in immunology2026
Dynamic regulation of hypoxia-associated regulatory CD39
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
B cells can suppress anti-tumor T cell responses, representing a potential mechanism of resistance to immunotherapy. Multiple Breg subsets have been described in humans and mice. Bregs inhibit anti-tumor immunity through cytokine secretion, immune checkpoint expression, and potentially adenosine generation, which collectively suppress effector T cells, and strengthen immunosuppressive signaling. Hypoxia is a hallmark of pancreatic ductal adenocarcinoma (PDAC) and contributes to immune dysregulation within the tumor microenvironment (TME); however, the effects of hypoxia on B cell subsets remain poorly defined. In this study, we investigated how hypoxic stress shapes regulatory B cell phenotype using murine PDAC models. We show that nearly half of intratumoral B cells are hypoxic, which also increased across systemic B cell compartments with tumor burden. Hypoxic B cells were enriched for CD39 and CD73 ectonucleotidases and suppressed T cell activation via adenosine receptor-dependent mechanisms. Hypoxia preferentially induced CD39
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