Novel tumor gene expression signatures improve the overall survival prediction efficiency over tumor mutation burden and PD-L1 expression in bladder carcinoma with checkpoint blockade immunotherapy.

Although immune checkpoint blockade therapy (ICBT) has revolutionized cancer treatment with good therapeutic response in a number of human cancers, including bladder cancer, many cancers still do not respond to ICBT. Analyzing genetic signatures helps the understanding of underlying biological mechanisms. Here, based on two cohorts of bladder cancer patients receiving ICBT, we identified three novel ICBT-associated signatures in the bladder cancer microenvironment, involving genomic stability, angiogenesis and RNA regulatory, which affect PD-L1 expression and patient response to ICBT. The combinations of these signatures with TMB or PD-L1 expression improved the overall survival prediction efficiency over TMB and PD-L1 expression alone for patients receiving ICBT. Moreover, we utilized two methods to search potential drugs or small-molecules that have an impact on ICBT-associated signatures. This study provides new molecular insight into ICBT response of bladder cancer and has the potential to improve the prediction accuracy for patients to benefit from ICBT.