{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T16:22:14Z","timestamp":1793982134086,"version":"4.8.0"},"reference-count":73,"publisher":"American Association for Cancer Research (AACR)","issue":"11","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["S10OD026880"],"award-info":[{"award-number":["S10OD026880"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004097","name":"Fondation ARC pour la Recherche sur le Cancer","doi-asserted-by":"crossref","award":["ANT201801285"],"award-info":[{"award-number":["ANT201801285"]}],"id":[{"id":"10.13039\/501100004097","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>It is currently accepted that cancer-associated fibroblasts (CAF) participate in T-cell exclusion from tumor nests. To unbiasedly test this, we used single-cell RNA sequencing coupled with multiplex imaging on a large cohort of lung tumors. We identified four main CAF populations, two of which are associated with T-cell exclusion: (i) MYH11+\u03b1SMA+ CAF, which are present in early-stage tumors and form a single cell layer lining cancer aggregates, and (ii) FAP+\u03b1SMA+ CAF, which appear in more advanced tumors and organize in patches within the stroma or in multiple layers around tumor nests. Both populations orchestrate a particular structural tissue organization through dense and aligned fiber deposition compared with T cell\u2013permissive CAF. Yet they produce distinct matrix molecules, including collagen IV (MYH11+\u03b1SMA+ CAF) and collagen XI\/XII (FAP+\u03b1SMA+ CAF). Hereby, we uncovered unique molecular programs of CAF driving T-cell marginalization, whose targeting should increase immunotherapy efficacy in patients bearing T cell\u2013excluded tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>The cellular and molecular programs driving T-cell marginalization in solid tumors remain unclear. Here, we describe two CAF populations associated with T-cell exclusion in human lung tumors. We demonstrate the importance of pairing molecular and spatial analysis of the tumor microenvironment, a prerequisite to developing new strategies targeting T cell\u2013excluding CAF.<\/jats:p>\n                    <jats:p>See related commentary by Sherman, p. 2501.<\/jats:p>\n                    <jats:p>This article is highlighted in the In This Issue feature, p. 2483<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-21-1714","type":"journal-article","created":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T15:50:07Z","timestamp":1661529007000},"page":"2606-2625","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":381,"title":["Spatial Positioning and Matrix Programs of Cancer-Associated Fibroblasts Promote T-cell Exclusion in Human Lung Tumors"],"prefix":"10.1158","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3889-2919","authenticated-orcid":false,"given":"John 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