{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:44:04Z","timestamp":1792061044788,"version":"4.4.0"},"reference-count":55,"publisher":"American Society for Clinical Investigation","issue":"18","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":61,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,16]]},"abstract":"<jats:p>The germinal center (GC) dark zone (DZ) and light zone represent distinct anatomical regions in lymphoid tissue where B cell proliferation, immunoglobulin diversification, and selection are coordinated. Diffuse large B cell lymphomas (DLBCLs) with DZ-like gene expression profiles exhibit poor outcomes, though the reasons are unclear and are not directly related to proliferation. Physiological DZs exhibit an exclusion of T cells, prompting exploration of whether T cell paucity contributes to DZ-like DLBCL. We used spatial transcriptomic approaches to achieve higher resolution of T cell spatial heterogeneity in the GC and to derive potential pathways that underlie T cell exclusion. We showed that T cell exclusion from the DZ was linked to DNA damage response (DDR) and chromatin compaction molecular features characterizing the spatial DZ signature, and that these programs were independent of activation-induced cytidine deaminase (AID) activity. As ATR is a key regulator of DDR, we tested its role in the T cell inhibitory DZ transcriptional imprint. ATR inhibition reversed not only the DZ transcriptional signature, but also DZ T cell exclusion in DZ-like DLBCL in vitro microfluidic models and in in vivo samples of murine lymphoid tissue. These findings highlight that ATR activity underpins a physiological scenario of immune silencing. ATR inhibition may reverse the immune-silent state and enhance T cell\u2013based immunotherapy in aggressive lymphomas with GC DZ\u2013like characteristics.<\/jats:p>","DOI":"10.1172\/jci187371","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T16:00:22Z","timestamp":1752768022000},"source":"Crossref","is-referenced-by-count":6,"title":["Aggressive B cell lymphomas retain ATR-dependent determinants of T cell exclusion from the germinal center dark zone"],"prefix":"10.1172","volume":"135","author":[{"given":"Valeria","family":"Cancila","sequence":"first","affiliation":[{"name":"Tumor Immunology Unit, Department of Health Sciences, University of Palermo, Palermo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Bertolazzi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Kore University of Enna, Enna, 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