Data from T cell–Mediated Development of Stromal Fibroblasts with an Immune-Enhancing Chemokine Profile

• DOI: 10.1158/2326-6066.c.6684962.v1
• Publication Date: 2023-06-07T15:40:24Z
• Authors: Ran Yan; Philip Moresco; Bruno Gegenhuber; Douglas T. Fearon
• Keywords: CXCL9; CCL5; CXCL16

<div>Abstract<p>Stromal fibroblasts reside in inflammatory tissues that are characterized by either immune suppression or activation. Whether and how adapt to these contrasting microenvironments remains unknown. Cancer-associated (CAF) mediate quiescence producing the chemokine CXCL12, which coats cancer cells suppress T-cell infiltration. We examined whether CAFs can also adopt an immune-promoting profile. Single-cell RNA sequencing of from mouse pancreatic adenocarcinomas identified a subpopulation with decreased expression <i>Cxcl12</i> increased T cell–attracting <i>Cxcl9</i> association TNFα IFNγ containing conditioned media activated CD8<sup>+</sup> converted stromal CXCL12<sup>+</sup>/CXCL9<sup>–</sup> immune-suppressive phenotype into CXCL12<sup>–</sup>/CXCL9<sup>+</sup> immune-activating phenotype. Recombinant acted together augment CXCL9 expression, whereas alone suppressed CXCL12 expression. This coordinated switch led infiltration <i>in vitro</i> chemotaxis assay. Our study demonstrates have phenotypic plasticity allows their adaptation tissue microenvironments.</p></div>