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HSP90A inhibition promotes anti-tumor immunity by reversing multi-modal resistance and stem-like property of immune-refractory tumors
DC Field | Value | Language |
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dc.contributor.author | 김재훈 | - |
dc.contributor.author | 조한별 | - |
dc.date.accessioned | 2021-05-21T17:07:00Z | - |
dc.date.available | 2021-05-21T17:07:00Z | - |
dc.date.issued | 2020-01 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/182714 | - |
dc.description.abstract | Cancer immunotherapy has emerged as a promising cancer treatment. However, the presence of immune-refractory tumor cells limits its clinical success by blocking amplification of anti-tumor immunity. Previously, we found that immune selection by immunotherapy drives the evolution of tumors toward multi-modal resistant and stem-like phenotypes via transcription induction of AKT co-activator TCL1A by NANOG. Here, we report a crucial role of HSP90A at the crossroads between NANOG-TCL1A axis and multi-aggressive properties of immune-edited tumor cells by identifying HSP90AA1 as a NANOG transcriptional target. Furthermore, we demonstrate that HSP90A potentiates AKT activation through TCL1A-stabilization, thereby contributing to the multi-aggressive properties in NANOGhigh tumor cells. Importantly, HSP90 inhibition sensitized immune-refractory tumor to adoptive T cell transfer as well as PD-1 blockade, and re-invigorated the immune cycle of tumor-reactive T cells. Our findings implicate that the HSP90A-TCL1A-AKT pathway ignited by NANOG is a central molecular axis and a potential target for immune-refractory tumor. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Nature Pub. Group | - |
dc.relation.isPartOf | NATURE COMMUNICATIONS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | HSP90 Heat-Shock Proteins / drug effects* | - |
dc.subject.MESH | HSP90 Heat-Shock Proteins / metabolism* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Immunity* | - |
dc.subject.MESH | Immunotherapy* | - |
dc.subject.MESH | Isoxazoles / pharmacology | - |
dc.subject.MESH | Mice, Inbred C57BL | - |
dc.subject.MESH | Mice, Inbred NOD | - |
dc.subject.MESH | Mice, SCID | - |
dc.subject.MESH | Nanog Homeobox Protein / metabolism | - |
dc.subject.MESH | Neoplastic Stem Cells / immunology* | - |
dc.subject.MESH | Neoplastic Stem Cells / metabolism* | - |
dc.subject.MESH | Programmed Cell Death 1 Receptor / metabolism | - |
dc.subject.MESH | Proto-Oncogene Proteins / metabolism | - |
dc.subject.MESH | Proto-Oncogene Proteins c-akt / metabolism | - |
dc.subject.MESH | Resorcinols / pharmacology | - |
dc.title | HSP90A inhibition promotes anti-tumor immunity by reversing multi-modal resistance and stem-like property of immune-refractory tumors | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Obstetrics and Gynecology (산부인과학교실) | - |
dc.contributor.googleauthor | Kwon-Ho Song | - |
dc.contributor.googleauthor | Se Jin Oh | - |
dc.contributor.googleauthor | Suyeon Kim | - |
dc.contributor.googleauthor | Hanbyoul Cho | - |
dc.contributor.googleauthor | Hyo-Jung Lee | - |
dc.contributor.googleauthor | Joon Seon Song | - |
dc.contributor.googleauthor | Joon-Yong Chung | - |
dc.contributor.googleauthor | Eunho Cho | - |
dc.contributor.googleauthor | Jaeyoon Lee | - |
dc.contributor.googleauthor | Seunghyun Jeon | - |
dc.contributor.googleauthor | Cassian Yee | - |
dc.contributor.googleauthor | Kyung-Mi Lee | - |
dc.contributor.googleauthor | Stephen M Hewitt | - |
dc.contributor.googleauthor | Jae-Hoon Kim | - |
dc.contributor.googleauthor | Seon Rang Woo | - |
dc.contributor.googleauthor | Tae Woo Kim | - |
dc.identifier.doi | 10.1038/s41467-019-14259-y | - |
dc.contributor.localId | A00876 | - |
dc.contributor.localId | A03921 | - |
dc.relation.journalcode | J02293 | - |
dc.identifier.eissn | 2041-1723 | - |
dc.identifier.pmid | 31992715 | - |
dc.contributor.alternativeName | Kim, Jae Hoon | - |
dc.contributor.affiliatedAuthor | 김재훈 | - |
dc.contributor.affiliatedAuthor | 조한별 | - |
dc.citation.volume | 11 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 562 | - |
dc.identifier.bibliographicCitation | NATURE COMMUNICATIONS, Vol.11(1) : 562, 2020-01 | - |
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