Matches in SemOpenAlex for { <https://semopenalex.org/work/W4296709712> ?p ?o ?g. }
- W4296709712 endingPage "4287" @default.
- W4296709712 startingPage "4274" @default.
- W4296709712 abstract "In multiple types of cancer, an increased frequency in myeloid-derived suppressor cells (MDSC) is associated with worse outcomes and poor therapeutic response. In the glioblastoma (GBM) microenvironment, monocytic (m) MDSCs represent the predominant subset. However, the molecular basis of mMDSC enrichment in the tumor microenvironment compared with granulocytic (g) MDSCs has yet to be determined. Here we performed the first broad epigenetic profiling of MDSC subsets to define underlying cell-intrinsic differences in behavior and found that enhanced gene accessibility of cell adhesion programs in mMDSCs is linked to their tumor-accelerating ability in GBM models upon adoptive transfer. Mouse and human mMDSCs expressed higher levels of integrin β1 and dipeptidyl peptidase-4 (DPP-4) compared with gMDSCs as part of an enhanced cell adhesion signature. Integrin β1 blockade abrogated the tumor-promoting phenotype of mMDSCs and altered the immune profile in the tumor microenvironment, whereas treatment with a DPP-4 inhibitor extended survival in preclinical GBM models. Targeting DPP-4 in mMDSCs reduced pERK signaling and their migration towards tumor cells. These findings uncover a fundamental difference in the molecular basis of MDSC subsets and suggest that integrin β1 and DPP-4 represent putative immunotherapy targets to attenuate myeloid cell-driven immune suppression in GBM.Epigenetic profiling uncovers cell adhesion programming as a regulator of the tumor-promoting functions of monocytic myeloid-derived suppressor cells in glioblastoma, identifying therapeutic targets that modulate the immune response and suppress tumor growth." @default.
- W4296709712 created "2022-09-23" @default.
- W4296709712 creator A5003058226 @default.
- W4296709712 creator A5004589257 @default.
- W4296709712 creator A5011812220 @default.
- W4296709712 creator A5014744090 @default.
- W4296709712 creator A5019942179 @default.
- W4296709712 creator A5021332876 @default.
- W4296709712 creator A5021893710 @default.
- W4296709712 creator A5022406235 @default.
- W4296709712 creator A5025139820 @default.
- W4296709712 creator A5035577264 @default.
- W4296709712 creator A5039175910 @default.
- W4296709712 creator A5039448543 @default.
- W4296709712 creator A5041530623 @default.
- W4296709712 creator A5047205736 @default.
- W4296709712 creator A5051304324 @default.
- W4296709712 creator A5055822465 @default.
- W4296709712 creator A5061010815 @default.
- W4296709712 creator A5062380805 @default.
- W4296709712 creator A5077223212 @default.
- W4296709712 date "2022-09-20" @default.
- W4296709712 modified "2023-10-01" @default.
- W4296709712 title "Distinct Cell Adhesion Signature Defines Glioblastoma Myeloid-Derived Suppressor Cell Subsets" @default.
- W4296709712 cites W1972916378 @default.
- W4296709712 cites W1975373367 @default.
- W4296709712 cites W1979594866 @default.
- W4296709712 cites W1989126519 @default.
- W4296709712 cites W1996203485 @default.
- W4296709712 cites W1999995687 @default.
- W4296709712 cites W2014677321 @default.
- W4296709712 cites W2019629273 @default.
- W4296709712 cites W2057650653 @default.
- W4296709712 cites W2068934982 @default.
- W4296709712 cites W2089929639 @default.
- W4296709712 cites W2102619694 @default.
- W4296709712 cites W2108234281 @default.
- W4296709712 cites W2109424201 @default.
- W4296709712 cites W2117131162 @default.
- W4296709712 cites W2117728670 @default.
- W4296709712 cites W2117757143 @default.
- W4296709712 cites W2131821161 @default.
- W4296709712 cites W2147000598 @default.
- W4296709712 cites W2161214956 @default.
- W4296709712 cites W2171808845 @default.
- W4296709712 cites W2179438025 @default.
- W4296709712 cites W2341539131 @default.
- W4296709712 cites W2511743252 @default.
- W4296709712 cites W2569426717 @default.
- W4296709712 cites W2581747126 @default.
- W4296709712 cites W2604805073 @default.
- W4296709712 cites W2612857912 @default.
- W4296709712 cites W2738946651 @default.
- W4296709712 cites W2750074602 @default.
- W4296709712 cites W2883808647 @default.
- W4296709712 cites W2891184788 @default.
- W4296709712 cites W2896013175 @default.
- W4296709712 cites W2945537500 @default.
- W4296709712 cites W2954317599 @default.
- W4296709712 cites W2961217357 @default.
- W4296709712 cites W2979472290 @default.
- W4296709712 cites W2987063621 @default.
- W4296709712 cites W2994525341 @default.
- W4296709712 cites W2997280954 @default.
- W4296709712 cites W3003523542 @default.
- W4296709712 cites W3006996572 @default.
- W4296709712 cites W3007604420 @default.
- W4296709712 cites W3010011098 @default.
- W4296709712 cites W3016404549 @default.
- W4296709712 cites W3029925672 @default.
- W4296709712 cites W3036384505 @default.
- W4296709712 cites W3046152640 @default.
- W4296709712 cites W3093231338 @default.
- W4296709712 cites W3114152106 @default.
- W4296709712 cites W3116206322 @default.
- W4296709712 cites W3164692211 @default.
- W4296709712 doi "https://doi.org/10.1158/0008-5472.can-21-3840" @default.
- W4296709712 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36126163" @default.
- W4296709712 hasPublicationYear "2022" @default.
- W4296709712 type Work @default.
- W4296709712 citedByCount "5" @default.
- W4296709712 countsByYear W42967097122023 @default.
- W4296709712 crossrefType "journal-article" @default.
- W4296709712 hasAuthorship W4296709712A5003058226 @default.
- W4296709712 hasAuthorship W4296709712A5004589257 @default.
- W4296709712 hasAuthorship W4296709712A5011812220 @default.
- W4296709712 hasAuthorship W4296709712A5014744090 @default.
- W4296709712 hasAuthorship W4296709712A5019942179 @default.
- W4296709712 hasAuthorship W4296709712A5021332876 @default.
- W4296709712 hasAuthorship W4296709712A5021893710 @default.
- W4296709712 hasAuthorship W4296709712A5022406235 @default.
- W4296709712 hasAuthorship W4296709712A5025139820 @default.
- W4296709712 hasAuthorship W4296709712A5035577264 @default.
- W4296709712 hasAuthorship W4296709712A5039175910 @default.
- W4296709712 hasAuthorship W4296709712A5039448543 @default.
- W4296709712 hasAuthorship W4296709712A5041530623 @default.
- W4296709712 hasAuthorship W4296709712A5047205736 @default.
- W4296709712 hasAuthorship W4296709712A5051304324 @default.