Characterization of hypoxia response patterns identified prognosis and immunotherapy response in bladder cancer

Intra-tumoral hypoxia and immunity are highly correlated with prognosis of tumor patients. Nonetheless, no studies have reported a systematic analysis of the relationship between hypoxia response and immunity in bladder cancer (BLCA). In this study, we comprehensively evaluated the hypoxia response patterns and their association with genomic and clinicopathological characteristics of 1,343 BLCA patients using unsupervised consensus clustering. Five hypoxia response patterns were defined, and the HPXscore was constructed using least absolute shrinkage and selection operator (LASSO)-Cox regression algorithms to represent the individual hypoxia response pattern. The low HPXscore group was characterized by immune activation and high DNA damage repair, which was referred to the immune-inflamed phenotype. However, activation of stromal-related pathways was observed in the high HPXscore group, which is recognized as T cell suppressive and more likely to be an immune-excluded phenotype. Furthermore, the HPXscore was an independent prognostic factor and could act as a good predictor for immunotherapeutic outcomes in BLCA. Thus, depicting a comprehensive landscape of the hypoxia characteristics may therefore help us to interpret the underlying mechanism of immune escape and shed light on the clinical application of hypoxia modification and immune checkpoints targeting immunotherapies for BLCA.