2026-06-14T05:08:11Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/258782025-12-18T12:57:21Zcom_20.500.12105_2273com_20.500.12105_2202col_20.500.12105_19571

00925njm 22002777a 4500 dc Casanova-Acebes, Maria author Grout, John A author Sirven, Philemon author Leader, Andrew M author Maskey, Shrisha author Hector, Eglantine author Puisieux, Isabelle author Steffan, Fiona author Cheng, Evan author Tung, Navpreet author Maurin, Mathieu author Vaineau, Romain author Karpf, Lea author Plaud, Martin author Begue, Anne-Laure author Ganesh, Koushik author Mesple, Jérémy author Casanova-Acebes, Maria author Tabachnikova, Alexandra author Keerthivasan, Shilpa author Lansky, Alona author Berichel, Jessica Le author Walker, Laura author Rahman, Adeeb H author Gnjatic, Sacha author Girard, Nicolas author Lefevre, Marine author Damotte, Diane author Adam, Julien author Martin, Jerome C author Wolf, Andrea author Flores, Raja M author Beasley, Mary Beth author Pradhan, Rachana author Muller, Soren author Marron, Thomas U author Turley, Shannon J author Merad, Miriam author Kenigsberg, Ephraim author Salmon, Hélène author 2022-11-02 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. 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. See related commentary by Sherman, p. 2501. This article is highlighted in the In This Issue feature, p. 2483. Cancer Discov . 2022 Nov 2;12(11):2606-2625. https://pmc.ncbi.nlm.nih.gov/articles/PMC9633420/pdf/nihms-1834329.pdf 36027053 https://hdl.handle.net/20.500.12105/25878 BASEMENT-MEMBRANES STROMAL CELLS EARLY-PHASE IMAGEN EXPRESSION MIGRATION INMUNITY LYMPH CITOKINE ANTIBODIE Spatial Positioning and Matrix Programs of Cancer-Associated Fibroblasts Promote T-cell Exclusion in Human Lung Tumors.