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Publication : Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade.

First Author  Miyai Y Year  2022
Journal  Life Sci Alliance Volume  5
Issue  6 PubMed ID  35236758
Mgi Jnum  J:322997 Mgi Id  MGI:7260853
Doi  10.26508/lsa.202101230 Citation  Miyai Y, et al. (2022) Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade. Life Sci Alliance 5(6):e202101230
abstractText  Cancer-associated fibroblasts (CAFs) are an integral component of the tumor microenvironment (TME). Most CAFs shape the TME toward an immunosuppressive milieu and attenuate the efficacy of immune checkpoint blockade (ICB) therapy. However, the detailed mechanism of how heterogeneous CAFs regulate tumor response to ICB therapy has not been defined. Here, we show that a recently defined CAF subset characterized by the expression of Meflin, a glycosylphosphatidylinositol-anchored protein marker of mesenchymal stromal/stem cells, is associated with survival and favorable therapeutic response to ICB monotherapy in patients with non-small cell lung cancer (NSCLC). The prevalence of Meflin-positive CAFs was positively correlated with CD4-positive T-cell infiltration and vascularization within non-small cell lung cancer tumors. Meflin deficiency and CAF-specific Meflin overexpression resulted in defective and enhanced ICB therapy responses in syngeneic tumors in mice, respectively. These findings suggest the presence of a CAF subset that promotes ICB therapy efficacy, which adds to our understanding of CAF functions and heterogeneity.
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