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- W4309656465 abstract "The ectonucleotidases CD39 and CD73 catalyze extracellular ATP to immunosuppressive adenosine, and as such, represent potential cancer targets. We investigated biological impacts of CD39 and CD73 in pancreatic ductal adenocarcinoma (PDAC) by studying clinical samples and experimental mouse tumors. Stromal CD39 and tumoral CD73 expression significantly associated with worse survival in human PDAC samples and abolished the favorable prognostic impact associated with the presence of tumor-infiltrating CD8+ T cells. In mouse transplanted KPC tumors, both CD39 and CD73 on myeloid cells, as well as CD73 on tumor cells, promoted polarization of infiltrating myeloid cells towards an M2-like phenotype, which enhanced tumor growth. CD39 on tumor-specific CD8+ T cells and pancreatic stellate cells also suppressed IFNγ production by T cells. Although therapeutic inhibition of CD39 or CD73 alone significantly delayed tumor growth in vivo, targeting of both ectonucleotidases exhibited markedly superior antitumor activity. CD73 expression on human and mouse PDAC tumor cells also protected against DNA damage induced by gemcitabine and irradiation. Accordingly, large-scale pharmacogenomic analyses of human PDAC cell lines revealed significant associations between CD73 expression and gemcitabine chemoresistance. Strikingly, increased DNA damage in CD73-deficient tumor cells associated with activation of the cGAS-STING pathway. Moreover, cGAS expression in mouse KPC tumor cells was required for antitumor activity of the CD73 inhibitor AB680 in vivo. Our study, thus, illuminates molecular mechanisms whereby CD73 and CD39 seemingly cooperate to promote PDAC progression." @default.
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- W4309656465 date "2022-11-21" @default.
- W4309656465 modified "2023-10-06" @default.
- W4309656465 title "CD73 Inhibits cGAS–STING and Cooperates with CD39 to Promote Pancreatic Cancer" @default.
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- W4309656465 cites W2949662834 @default.
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- W4309656465 cites W2986950076 @default.
- W4309656465 cites W2995171541 @default.
- W4309656465 cites W2996396452 @default.
- W4309656465 cites W3002753972 @default.
- W4309656465 cites W3004193473 @default.
- W4309656465 cites W3005305333 @default.
- W4309656465 cites W3018073147 @default.
- W4309656465 cites W3023906975 @default.
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- W4309656465 cites W3127873789 @default.
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- W4309656465 cites W3141896073 @default.
- W4309656465 cites W3146625365 @default.
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- W4309656465 doi "https://doi.org/10.1158/2326-6066.cir-22-0260" @default.
- W4309656465 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36409930" @default.
- W4309656465 hasPublicationYear "2022" @default.
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