NANOG confers resistance to complement-dependent cytotoxicity in immune-edited tumor cells through up-regulating CD59

Autor: Sung Wook Son, Eunho Cho, Hanbyoul Cho, Seon Rang Woo, Hyo-Jung Lee, Se Jin Oh, Suyeon Kim, Jae-Hoon Kim, Eun Joo Chung, Joon-Yong Chung, Min Gyu Kim, Kwon-Ho Song, Tae Woo Kim
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Scientific Reports, Vol 12, Iss 1, Pp 1-10 (2022)
Druh dokumentu: article
ISSN: 2045-2322
96540362
DOI: 10.1038/s41598-022-12692-6
Popis: 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.
Databáze: Directory of Open Access Journals
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