{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:13:59Z","timestamp":1789769639763,"version":"4.0.1"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>High levels of extracellular adenosine, highly abundant in the tumor microenvironment, promote immune suppression mainly through the A2AR expressed by tumor-infiltrating immune cells. Given the importance of tumor-infiltrating B and plasma cells (PCs) in antitumor responses, we investigated the effect of A2AR on human B cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed quantitative mass spectrometry imaging followed by GeoMx analysis on 10 tumor samples. Immunohistochemistry, multiplex immunofluorescence and scRNA-seq were used to assess A2AR expression on tumor and tonsillar B cells.\n                      <jats:italic>In vitro<\/jats:italic>\n                      differentiated B cells and sorted tonsillar B cells were stimulated in the presence of the A2AR agonist CGS-21680 with or without the A2AR antagonist inupadenant, and analysed by flow cytometry, LegendPLEX and scRNA-seq. The\n                      <jats:italic>in vivo<\/jats:italic>\n                      effect of inupadenant was assessed using Visium on tumor biopsies from five cancer patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The frequency of PCs was the most negatively affected by adenosine among the immune cells present in the tumor microenvironment. Furthermore, both tonsillar and tumor-associated B cells, including germinal center (GC)-like B cells, PCs and plasma blasts, collectively referred to as antibody-secreting cells (ASCs), expressed high levels of A2AR. Triggering of A2AR inhibited B cell maturation into ASCs and immunoglobulin production\n                      <jats:italic>in vitro<\/jats:italic>\n                      , and impaired upregulation of PC genes upon stimulation. These effects were restored by inupadenant (EOS100850), a potent and highly selective small molecule A2AR antagonist. Spatial transcriptomics analysis of tumor biopsies from patients treated with inupadenant revealed that ASCs specifically increased in tertiary lymphoid structures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Altogether, these data demonstrate that A2AR plays a key role in adenosine-mediated inhibition of B cell maturation toward ASCs through a B cell-intrinsic mechanism, and that this effect is fully reverted by inupadenant.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1702402","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T06:29:15Z","timestamp":1765780155000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Inhibition of A2AR alleviates adenosine-mediated suppression of plasma cell 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