Cancer-associated MSC drive tumor immune exclusion and resistance to immunotherapy, which can be overcome by Hedgehog inhibition.

ABSTRACT: We investigated the impact of cancer-associated mesenchymal stem cells (CA-MSCs) on ovarian tumor immunity. In patient samples, CA-MSC presence inversely correlates with the presence of intratumoral CD8⁺ T cells. Using an immune “hot” mouse ovarian cancer model, we found that CA-MSCs drive CD8⁺ T cell tumor immune exclusion and reduce response to anti–PD-L1 immune checkpoint inhibitor (ICI) via secretion of numerous chemokines (Ccl2, Cx3cl1, and Tgf-β1), which recruit immune-suppressive CD14⁺Ly6C⁺Cx3cr1⁺ monocytic cells and polarize macrophages to an immune suppressive Ccr2^hiF4/80⁺Cx3cr1⁺CD206⁺ phenotype. Both monocytes and macrophages express high levels of transforming growth factor β–induc

SUBMITTER: Cascio S 

PROVIDER: S-EPMC8589308 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature