{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T20:50:57Z","timestamp":1786308657764,"version":"build-2736575974"},"posted":{"date-parts":[[2026,4,12]]},"group-title":"Immunology","reference-count":57,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National Cancer Institute of the US National Institutes of Health","award":["R01CA190700"],"award-info":[{"award-number":["R01CA190700"]}]},{"name":"National Cancer Institute of the National Institutes of Health Cancer Center","award":["P30CA91842"],"award-info":[{"award-number":["P30CA91842"]}]},{"name":"Stand Up to Cancer-Lustgarten Foundation"},{"name":"Pancreatic Cancer Foundation Convergence Dream Team Translational Research Grant"},{"DOI":"10.13039\/100014547","name":"Parker Institute for Cancer Immunotherapy","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014547","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,10]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>Spatially organized immune hubs of T cells and antigen-presenting cells (APCs) have been linked to immune checkpoint therapy (ICT) efficacy, yet the mechanisms underlying their function remain unclear. Using CODEX multiplex imaging, we longitudinally characterized the dynamic evolution of intratumoral cellular neighborhoods (CN) defined by \u201ctriad\u201d interactions of CD4\u207a and CD8\u207a T cells with two distinct myeloid APC populations: cDC1s and IFN\u03b3\u2013activated macrophages. We termed this CN the immunity-promoting CN (IP-CN) and tracked its progressive development during tumor rejection induced by \u03b1-CTLA-4\/\u03b1-PD-1 therapy. A coordinated IFN\u03b3 and TNF\u03b1 signaling signature accompanied the IP-CN assembly. Over time, the IP-CN underwent functional maturation, forming specialized sub-neighborhoods that compartmentalized proliferating T cells at the tumor periphery versus cytotoxic T effector cells interacting with tumor cell targets. Our findings reveal a spatiotemporal mechanism by which the IP-CN sustains and amplifies cytotoxic T cell responses, demonstrating how T cell\u2013APC neighborhoods orchestrate tumor immunity.<\/jats:p>","DOI":"10.64898\/2026.04.08.716779","type":"posted-content","created":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T09:30:12Z","timestamp":1775986212000},"source":"Crossref","is-referenced-by-count":1,"title":["Immune Checkpoint Therapy Drives Maturation of a Cellular Neighborhood Nucleated by T Cell-APC Triads Enabling Spatially Compartmentalized Tumor Immunity"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8071-5880","authenticated-orcid":false,"given":"Ruan F. Vieira","family":"Medrano","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine"},{"name":"The Andrew M. and Jane M. 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