Inhibition of METTL3 Results in a Cell-Intrinsic Interferon Response That Enhances Antitumor Immunity

抑制 METTL3 可引发细胞内在干扰素反应,从而增强抗肿瘤免疫力

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作者:Andrew A Guirguis #, Yaara Ofir-Rosenfeld #, Kathy Knezevic, Wesley Blackaby, David Hardick, Yih-Chih Chan, Ali Motazedian, Andrea Gillespie, Dane Vassiliadis, Enid Y N Lam, Kevin Tran, Byron Andrews, Michael E Harbour, Lina Vasiliauskaite, Claire J Saunders, Georgia Tsagkogeorga, Aleksandra Azevedo

Significance

This work demonstrates that METTL3 inhibition stimulates a cell-intrinsic interferon response through dsRNA formation. This immunomodulatory mechanism is distinct from current immunotherapeutic agents and provides the molecular rationale for combination with anti-PD-1 immune-checkpoint blockade to augment antitumor immunity. This article is featured in Selected Articles from This Issue, p. 2109.

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