TY - JOUR T1 - Alterations in DNA damage response and repair genes as potential biomarkers for immune checkpoint blockade in gastrointestinal cancer JF - Cancer Biology & Medicine JO - Cancer Biology & Medicine SP - 1139 LP - 1149 DO - 10.20892/j.issn.2095-3941.2020.0708 VL - 19 IS - 8 AU - Yujiao Wang AU - Xi Jiao AU - Shuang Li AU - Huan Chen AU - Xin Wei AU - Chang Liu AU - Jifang Gong AU - Xiaotian Zhang AU - Xicheng Wang AU - Zhi Peng AU - Changsong Qi AU - Zhenghang Wang AU - Yanni Wang AU - Na Zhuo AU - Jianling Zou AU - Henghui Zhang AU - Jian Li AU - Lin Shen AU - Zhihao Lu Y1 - 2022/08/15 UR - http://www.cancerbiomed.org/content/19/8/1139.abstract N2 - Objective: Immune checkpoint inhibitors (ICIs) have achieved remarkable results in cancer treatments. However, there is no effective predictive biomarker for gastrointestinal (GI) cancer.Methods: We conducted integrative analyses of the genomic and survival data of ICI-treated GI cancer patients from the Memorial Sloan Kettering Cancer Center cohort (MSK-GI, n = 227), the Janjigian cohort (n = 40), and the Peking University Cancer Hospital & Institute cohort (PUCH, n = 80) to determine the possible associations between DNA damage response and repair (DDR) gene mutations and clinical outcomes. Data from The Cancer Genome Atlas database were analyzed to determine the possible correlations between DDR gene mutations and the tumor microenvironment.Results: In the MSK cohort, the presence of ≥ 2 DDR gene mutations was correlated with prolonged overall survival (OS). The Janjigian and PUCH cohorts further confirmed that subgroups with ≥ 2 DDR gene mutations displayed a prolonged OS and a higher durable clinical benefit. Furthermore, the DDR gene mutation load could be considered as an independent prognostic factor, and exhibited a potential predictive value for survival in GI cancer patients treated with ICIs. Mechanistically, we showed that the presence of ≥ 2 DDR gene mutations was correlated with higher levels of tumor mutation burden, neoantigen, and T cell infiltration.Conclusions: The DDR gene mutation status was correlated with favorable clinical outcomes in GI cancer patients receiving ICIs, which could serve as a potential biomarker to guide patient selection for immunotherapy. ER -