Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Scientific reports, 2022-05, Vol.12 (1), p.8652-8652, Article 8652

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2022

Quelle

Open access e-journals

Beschreibungen/Notizen

• 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.