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Protein Kinase A Catalytic Subunit Is a Molecular Switch that Promotes the Pro-tumoral Function of Macrophages
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Na, Yi Rang | - |
dc.contributor.author | Kwon, Jung Won | - |
dc.contributor.author | Kim, Da Young | - |
dc.contributor.author | Chung, Hyewon | - |
dc.contributor.author | Song, Juha | - |
dc.contributor.author | Jung, Daun | - |
dc.contributor.author | Quan, Hailian | - |
dc.contributor.author | Kim, Daesik | - |
dc.contributor.author | Kim, Jin-Soo | - |
dc.contributor.author | Ju, Young Wook | - |
dc.contributor.author | Han, Wonshik | - |
dc.contributor.author | Ryu, Han Suk | - |
dc.contributor.author | Lee, Yun-Sang | - |
dc.contributor.author | Hong, Jung Joo | - |
dc.contributor.author | Seok, Seung Hyeok | - |
dc.date.accessioned | 2022-04-20T10:55:48Z | - |
dc.date.available | 2022-04-20T10:55:48Z | - |
dc.date.created | 2020-06-02 | - |
dc.date.created | 2020-06-02 | - |
dc.date.created | 2020-06-02 | - |
dc.date.issued | 2020-05 | - |
dc.identifier.citation | Cell Reports, Vol.31 No.6, p. 107643 | - |
dc.identifier.issn | 2211-1247 | - |
dc.identifier.other | 102110 | - |
dc.identifier.uri | https://hdl.handle.net/10371/179117 | - |
dc.description.abstract | As 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.language | 영어 | - |
dc.publisher | Cell Press | - |
dc.title | Protein Kinase A Catalytic Subunit Is a Molecular Switch that Promotes the Pro-tumoral Function of Macrophages | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 류한석 | - |
dc.contributor.AlternativeAuthor | 한원식 | - |
dc.contributor.AlternativeAuthor | 석승혁 | - |
dc.contributor.AlternativeAuthor | 김진수 | - |
dc.identifier.doi | 10.1016/j.celrep.2020.107643 | - |
dc.citation.journaltitle | Cell Reports | - |
dc.identifier.wosid | 000533147000023 | - |
dc.identifier.scopusid | 2-s2.0-85084345620 | - |
dc.citation.number | 6 | - |
dc.citation.startpage | 107643 | - |
dc.citation.volume | 31 | - |
dc.identifier.sci | 000533147000023 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Kim, Jin-Soo | - |
dc.contributor.affiliatedAuthor | Han, Wonshik | - |
dc.contributor.affiliatedAuthor | Ryu, Han Suk | - |
dc.contributor.affiliatedAuthor | Lee, Yun-Sang | - |
dc.contributor.affiliatedAuthor | Seok, Seung Hyeok | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | BREAST-CANCER METASTASIS | - |
dc.subject.keywordPlus | MYELOID CELLS | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | POLARIZATION | - |
dc.subject.keywordPlus | CHEMOTHERAPY | - |
dc.subject.keywordPlus | THERAPY | - |
dc.subject.keywordPlus | CREB | - |
dc.subject.keywordPlus | PKA | - |
dc.subject.keywordPlus | PROGRESSION | - |
dc.subject.keywordPlus | RESPONSES | - |
dc.subject.keywordAuthor | immunotherapy | - |
dc.subject.keywordAuthor | molecular target | - |
dc.subject.keywordAuthor | protein kinase A catalytic subunit | - |
dc.subject.keywordAuthor | tumor microenvironment | - |
dc.subject.keywordAuthor | tumor-associated macrophage | - |
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