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Distinct cell adhesion signature defines glioblastoma myeloid-derived suppressor cell subsets

ABSTRACT: Increased myeloid-derived suppressor cell (MDSC) frequency is associated with worse outcomes and poor therapeutic response in multiple types of cancer. In the glioblastoma (GBM) microenvironment, monocytic (m) MDSCs represent the predominant subset. However, the molecular basis of mMDSC enrichment in the tumor microenvironment compared to granulocytic (g) MDSCs has yet to be determined. Here we performed first broad epigenetic profiling of MDSC subsets to define underlying cell-intrinsic differences in their behavior and found that mMDSCs and gMDSCs display differences in their tumor-accelerating ability, with mMDSCs driving tumor growth in GBM models. Epigenetic assessments revealed enhanced gene accessibility for cell adhesion programs in mMDSCs and higher integrin b1 expression and function in mouse and human mMDSCs. Integrin b1 blockage abrogated the tumor-promoting phenotype of mMDSCs and altered the immune profile in the tumor microenvironment. These findings suggest that integrin b1 expression underlies the enrichment of mMDSCs in tumors and represents a putative immunotherapy target to attenuate myeloid cell-driven immune suppression in GBM.

ORGANISM(S): Mus musculus

PROVIDER: GSE206551 | GEO | 2022/06/26

REPOSITORIES: GEO

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