NANOG confers resistance to complement-dependent cytotoxicity in immune-edited tumor cells through up-regulating CD59open access
- Authors
- Son, Sung Wook; Cho, Eunho; Cho, Hanbyoul; Woo, Seon Rang; Lee, Hyo-Jung; Oh, Se Jin; Kim, Suyeon; Kim, Jae-Hoon; Chung, Eun Joo; Chung, Joon-Yong; Kim, Min Gyu; Song, Kwon-Ho; Kim, Tae Woo
- Issue Date
- 23-5월-2022
- Publisher
- NATURE PORTFOLIO
- Citation
- SCIENTIFIC REPORTS, v.12, no.1
- Indexed
- SCIE
SCOPUS
- Journal Title
- SCIENTIFIC REPORTS
- Volume
- 12
- Number
- 1
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/143049
- DOI
- 10.1038/s41598-022-12692-6
- ISSN
- 2045-2322
- Abstract
- Cancer immunoediting drives the adaptation of tumor cells to host immune surveillance. Previously, we have demonstrated that immunoediting driven by cytotoxic T lymphocytes (CTLs) enriches NANOG(+) tumor cells with immune-refractory properties. Here, we found that CTL-mediated immune pressure triggered cross-resistance of tumor cells to the complement system, a part of the innate immune system. In this process, NANOG upregulated the membrane-bound complement regulatory protein (mCRP) CD59 through promoter occupancy, thereby contributing to the resistance of tumor cells against complement-dependent cytotoxicity (CDC). Notably, targeting of NANOG sensitized the immune-refractory tumor cells to trastuzumab-mediated CDC. Collectively, our results revealed a possible mechanism through which selection imposed by T-cell based immunotherapy triggered complement-resistant phenotypes in the tumor microenvironment (TME), by establishing a firm molecular link between NANOG and CD59 in immune-edited tumor cells. We believe these results hold important implications for the clinical application of CDC-mediated therapeutic antibody.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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