AMPK promotes antitumor immunity by downregulating PD-1 in regulatory T cells via the HMGCR/p38 signaling pathway
DC Field | Value | Language |
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dc.contributor.author | Pokhrel, Ram Hari | - |
dc.contributor.author | Acharya, Suman | - |
dc.contributor.author | Ahn, Jae-Hee | - |
dc.contributor.author | Gu, Ye | - |
dc.contributor.author | Pandit, Mahesh | - |
dc.contributor.author | Kim, Jong-Oh | - |
dc.contributor.author | Park, Yun-Yong | - |
dc.contributor.author | Kang, Ben | - |
dc.contributor.author | Ko, Hyun-Jeong | - |
dc.contributor.author | Chang, Jae-Hoon | - |
dc.date.accessioned | 2023-03-08T10:11:59Z | - |
dc.date.available | 2023-03-08T10:11:59Z | - |
dc.date.issued | 2021-10-14 | - |
dc.identifier.issn | 1476-4598 | - |
dc.identifier.issn | 1476-4598 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/62121 | - |
dc.description.abstract | Background AMP-activated protein kinase (AMPK) is a metabolic sensor that maintains energy homeostasis. AMPK functions as a tumor suppressor in different cancers; however, its role in regulating antitumor immunity, particularly the function of regulatory T cells (Tregs), is poorly defined. Methods AMPK alpha 1(fl/fl)Foxp3(YFP-Cre), Foxp3(YFP-Cre), Rag1(-/-), and C57BL/6 J mice were used for our research. Flow cytometry and cell sorting, western blotting, immuno-precipitation, immuno-fluorescence, glycolysis assay, and qRT-PCR were used to investigate the role of AMPK in suppressing programmed cell death 1 (PD-1) expression and for mechanistic investigation. Results The deletion of the AMPK alpha 1 subunit in Tregs accelerates tumor growth by increasing the expression of PD-1. Metabolically, loss of AMPK in Tregs promotes glycolysis and the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), a key enzyme of the mevalonate pathway. Mechanistically, AMPK activates the p38 mitogen-activated protein kinase (MAPK) that phosphorylates glycogen synthase kinase-3 beta (GSK-3 beta), inhibiting the expression of PD-1 in Tregs. Conclusion Our study identified an AMPK regulatory mechanism of PD-1 expression via the HMGCR/p38 MAPK/GSK3 beta signaling pathway. We propose that the AMPK activator can display synergic antitumor effect in murine tumor models, supporting their potential clinical use when combined with anti-PD-1 antibody, anti-CTLA-4 antibody, or a HMGCR inhibitor. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | BMC | - |
dc.title | AMPK promotes antitumor immunity by downregulating PD-1 in regulatory T cells via the HMGCR/p38 signaling pathway | - |
dc.type | Article | - |
dc.identifier.doi | 10.1186/s12943-021-01420-9 | - |
dc.identifier.bibliographicCitation | MOLECULAR CANCER, v.20, no.1 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000707944400002 | - |
dc.identifier.scopusid | 2-s2.0-85117277371 | - |
dc.citation.number | 1 | - |
dc.citation.title | MOLECULAR CANCER | - |
dc.citation.volume | 20 | - |
dc.type.docType | Article | - |
dc.publisher.location | 영국 | - |
dc.subject.keywordAuthor | Tregs | - |
dc.subject.keywordAuthor | Tumor | - |
dc.subject.keywordAuthor | PD-1 | - |
dc.subject.keywordAuthor | AMPK | - |
dc.subject.keywordAuthor | HMGCR | - |
dc.subject.keywordAuthor | Compound C | - |
dc.subject.keywordAuthor | AICAR | - |
dc.subject.keywordPlus | ACTIVATED PROTEIN-KINASE | - |
dc.subject.keywordPlus | ENERGY SENSOR | - |
dc.subject.keywordPlus | P38 MAPK | - |
dc.subject.keywordPlus | INACTIVATION | - |
dc.subject.keywordPlus | MELANOMA | - |
dc.subject.keywordPlus | BLOCKADE | - |
dc.subject.keywordPlus | GROWTH | - |
dc.subject.keywordPlus | INTERLEUKIN-10 | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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