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• W4362553658 abstract "<div>Abstract<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⁺αSMA⁺ CAF, which are present in early-stage tumors and form a single cell layer lining cancer aggregates, and (ii) FAP⁺αSMA⁺ 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–permissive CAF. Yet they produce distinct matrix molecules, including collagen IV (MYH11⁺αSMA⁺ CAF) and collagen XI/XII (FAP⁺αSMA⁺ CAF). Hereby, we uncovered unique molecular programs of CAF driving T-cell marginalization, whose targeting should increase immunotherapy efficacy in patients bearing T cell–excluded tumors.</p>Significance:<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–excluding CAF.</p><p><i><a href=https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-22-0944 target=_blank>See related commentary by Sherman, p. 2501</a>.</i></p><p><i><a href=https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-12-11-ITI target=_blank>This article is highlighted in the In This Issue feature, p. 2483</a></i></p></div>" @default.
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• W4362553658 date "2023-04-04" @default.
• W4362553658 modified "2023-10-16" @default.
• W4362553658 title "Data from Spatial Positioning and Matrix Programs of Cancer-Associated Fibroblasts Promote T-cell Exclusion in Human Lung Tumors" @default.
• W4362553658 doi "https://doi.org/10.1158/2159-8290.c.6549735" @default.
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