HSP90A inhibition promotes anti-tumor immunity by reversing multi-modal resistance and stem-like property of immune-refractory tumors
- Authors
- Song, Kwon-Ho; Oh, Se Jin; Kim, Suyeon; Cho, Hanbyoul; Lee, Hyo-Jung; Song, Joon Seon; Chung, Joon-Yong; Cho, Eunho; Lee, Jaeyoon; Jeon, Seunghyun; Yee, Cassian; Lee, Kyung-Mi; Hewitt, Stephen M.; Kim, Jae-Noon; Woo, Seon Rang; Kim, Tae Woo
- Issue Date
- 28-1월-2020
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- NATURE COMMUNICATIONS, v.11, no.1
- Indexed
- SCIE
SCOPUS
- Journal Title
- NATURE COMMUNICATIONS
- Volume
- 11
- Number
- 1
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/57943
- DOI
- 10.1038/s41467-019-14259-y
- ISSN
- 2041-1723
- 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.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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