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Immune checkpoint inhibitors (ICIs) have shown promising results in bladder cancer (BC). However, only some patients respond to ICIs. DNA repair defects (DDR) play an important role in the therapeutic response of bladder cancer. Therefore, we aimed to elucidate the association between ICIs in bladder cancer and ataxia telangiectasia mutated (ATM), a core component of the DNA repair system. From a collected immunotherapy cohort (n = 210) and The Cancer Genome Atlas (TCGA)-Bladder cancer cohort, which were both retrieved from publicly available resources, we performed a series of analyses to evaluate the prognostic value and potential mechanism of ATM in bladder cancer immunotherapy. We found that ATM-mutant (ATM-MT) bladder cancer patients derived greater benefit from ICIs overall survival (OS), hazard ratio (HR) = 0.28, [95% confidence interval (CI), 0.16 to 0.51, P = 0.007] and showed a higher mutation load (P P 1, P P P P < 0.05), including cisplatin and BMS-536924, an IGF-1R inhibitor. Our results demonstrate the importance of ATM as a prognostic signature in bladder cancer and reveal that ATM may impact the effects of ICIs by acting on the tumor immune microenvironment.
Yi et al. (Fri,) studied this question.