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 | Song, Kwon-Ho | - |
dc.contributor.author | Oh, Se Jin | - |
dc.contributor.author | Kim, Suyeon | - |
dc.contributor.author | Cho, Hanbyoul | - |
dc.contributor.author | Lee, Hyo-Jung | - |
dc.contributor.author | Song, Joon Seon | - |
dc.contributor.author | Chung, Joon-Yong | - |
dc.contributor.author | Cho, Eunho | - |
dc.contributor.author | Lee, Jaeyoon | - |
dc.contributor.author | Jeon, Seunghyun | - |
dc.contributor.author | Yee, Cassian | - |
dc.contributor.author | Lee, Kyung-Mi | - |
dc.contributor.author | Hewitt, Stephen M. | - |
dc.contributor.author | Kim, Jae-Noon | - |
dc.contributor.author | Woo, Seon Rang | - |
dc.contributor.author | Kim, Tae Woo | - |
dc.date.accessioned | 2021-08-31T12:04:11Z | - |
dc.date.available | 2021-08-31T12:04:11Z | - |
dc.date.created | 2021-06-19 | - |
dc.date.issued | 2020-01-28 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/57943 | - |
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 NANOG(high) 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.language | English | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.subject | ACQUIRED-RESISTANCE | - |
dc.subject | CANCER-IMMUNITY | - |
dc.subject | PD-1 BLOCKADE | - |
dc.subject | T-CELLS | - |
dc.subject | GENE | - |
dc.subject | TRANSCRIPTION | - |
dc.subject | MECHANISM | - |
dc.subject | BINDING | - |
dc.subject | AKT | - |
dc.subject | HEAT-SHOCK-PROTEIN-90 | - |
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.affiliatedAuthor | Oh, Se Jin | - |
dc.contributor.affiliatedAuthor | Kim, Tae Woo | - |
dc.identifier.doi | 10.1038/s41467-019-14259-y | - |
dc.identifier.scopusid | 2-s2.0-85078468258 | - |
dc.identifier.wosid | 000563506800001 | - |
dc.identifier.bibliographicCitation | NATURE COMMUNICATIONS, v.11, no.1 | - |
dc.relation.isPartOf | NATURE COMMUNICATIONS | - |
dc.citation.title | NATURE COMMUNICATIONS | - |
dc.citation.volume | 11 | - |
dc.citation.number | 1 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | ACQUIRED-RESISTANCE | - |
dc.subject.keywordPlus | CANCER-IMMUNITY | - |
dc.subject.keywordPlus | PD-1 BLOCKADE | - |
dc.subject.keywordPlus | T-CELLS | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordPlus | TRANSCRIPTION | - |
dc.subject.keywordPlus | MECHANISM | - |
dc.subject.keywordPlus | BINDING | - |
dc.subject.keywordPlus | AKT | - |
dc.subject.keywordPlus | HEAT-SHOCK-PROTEIN-90 | - |
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