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Protein Kinase A Catalytic Subunit Is a Molecular Switch that Promotes the Pro-tumoral Function of Macrophages

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dc.contributor.authorNa, Yi Rang-
dc.contributor.authorKwon, Jung Won-
dc.contributor.authorKim, Da Young-
dc.contributor.authorChung, Hyewon-
dc.contributor.authorSong, Juha-
dc.contributor.authorJung, Daun-
dc.contributor.authorQuan, Hailian-
dc.contributor.authorKim, Daesik-
dc.contributor.authorKim, Jin-Soo-
dc.contributor.authorJu, Young Wook-
dc.contributor.authorHan, Wonshik-
dc.contributor.authorRyu, Han Suk-
dc.contributor.authorLee, Yun-Sang-
dc.contributor.authorHong, Jung Joo-
dc.contributor.authorSeok, Seung Hyeok-
dc.date.accessioned2022-04-20T10:55:48Z-
dc.date.available2022-04-20T10:55:48Z-
dc.date.issued2020-05-
dc.identifier.citationCell Reports, Vol.31 No.6, p. 107643-
dc.identifier.issn2211-1247-
dc.identifier.other102110-
dc.identifier.urihttps://hdl.handle.net/10371/179117-
dc.description.abstractAs current therapies benefit only a minority of cancer patients, additional therapeutic targets are needed. Tumor-associated macrophages (TAMs) have attracted attention for improving therapeutic responses, yet regulatory strategies remain elusive. Here, we show that the protein kinase A catalytic subunit (PKA-C) acts as a molecular switch, inducing a pro-tumoral immunosuppressive macrophage phenotype within tumors. In human and murine breast cancer, overactivated PKA in TAMs creates a detrimental microenvironment for cancer progression by inducing vascular endothelial growth factor A (VEGFA), interleukin-10 (IL-10), and macrophage-derived arginase 1 (ARG1) expression. Macrophages with genetic deletion of PKA-C are prone to be pro-inflammatory, suggesting a possible immunotherapeutic target. Delivery of liposomal PKA inhibitor facilitates tumor regression and abrogates pro-tumoral TAM functions in mice. The therapeutic effect of targeting PKA is pronounced when combined with alpha CTLA-4 antibody, increasing cluster of differentiation 8 (CD8)(+)GranzymeB(+) T cells by about 60-fold. Our findings demonstrate critical roles of TAM PKA-C in tumor progression and suggest that targeting PKA-C efficiently augments cancer treatment responses.-
dc.titleProtein Kinase A Catalytic Subunit Is a Molecular Switch that Promotes the Pro-tumoral Function of Macrophages-
dc.typeArticle-
dc.contributor.AlternativeAuthor류한석-
dc.contributor.AlternativeAuthor한원식-
dc.contributor.AlternativeAuthor석승혁-
dc.contributor.AlternativeAuthor김진수-
dc.identifier.doi10.1016/j.celrep.2020.107643-
dc.citation.journaltitleCell Reports-
dc.identifier.scopusid2-s2.0-85084345620-
dc.citation.number6-
dc.citation.startpage107643-
dc.citation.volume31-
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S2211124720305969?via%3Dihub-
dc.identifier.rimsid102110-
dc.identifier.sci000533147000023-
dc.description.isOpenAccessY-
dc.contributor.affiliatedAuthorKim, Jin-Soo-
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