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

Abstract

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