DNA Sensing in Mismatch Repair-Deficient Tumor Cells Is Essential for Anti-tumor Immunity.
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ABSTRACT:
SUBMITTER: Lu C
PROVIDER: S-EPMC9477183 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
DNA Sensing in Mismatch Repair-Deficient Tumor Cells Is Essential for Anti-tumor Immunity.
Lu Changzheng C Guan Junhong J Lu Steve S Jin Qihuang Q Rousseau Benoit B Lu Tianshi T Stephens Dennis D Zhang Hongyi H Zhu Jiankun J Yang Mingming M Ren Zhenhua Z Liang Yong Y Liu Zhida Z Han Chuanhui C Liu Longchao L Cao Xuezhi X Zhang Anli A Qiao Jian J Batten Kimberly K Chen Mingyi M Castrillon Diego H DH Wang Tao T Li Bo B Diaz Luis A LA Li Guo-Min GM Fu Yang-Xin YX
Cancer cell 20201217 1
Increased neoantigens in hypermutated cancers with DNA mismatch repair deficiency (dMMR) are proposed as the major contributor to the high objective response rate in anti-PD-1 therapy. However, the mechanism of drug resistance is not fully understood. Using tumor models defective in the MMR gene Mlh1 (dMLH1), we show that dMLH1 tumor cells accumulate cytosolic DNA and produce IFN-β in a cGAS-STING-dependent manner, which renders dMLH1 tumors slowly progressive and highly sensitive to checkpoint ...[more]
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