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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number8652
JournalScientific reports
Volume12
Issue number1
DOIs
Publication statusPublished - 2022 Dec

ASJC Scopus subject areas

  • General

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