Cao Rui, Ma Bo, Wang Gang, Xiong Yaoyi, Tian Ye, Yuan Lushun
Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Department of Stomatology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
Mol Ther Oncolytics. 2021 Jul 2;22:277-293. doi: 10.1016/j.omto.2021.06.011. eCollection 2021 Sep 24.
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.
肿瘤内缺氧与免疫状态与肿瘤患者的预后高度相关。然而，尚无研究报道对膀胱癌（BLCA）中缺氧反应与免疫之间的关系进行系统分析。在本研究中，我们采用无监督一致性聚类方法，全面评估了1343例BLCA患者的缺氧反应模式及其与基因组和临床病理特征的关联。定义了五种缺氧反应模式，并使用最小绝对收缩和选择算子（LASSO）-Cox回归算法构建了HPXscore，以代表个体的缺氧反应模式。低HPXscore组的特征是免疫激活和高DNA损伤修复能力，这被称为免疫炎症表型。然而，在高HPXscore组中观察到基质相关通路的激活，这被认为具有T细胞抑制作用，更可能是一种免疫排除表型。此外，HPXscore是一个独立的预后因素，并且可以作为BLCA免疫治疗结果的良好预测指标。因此，描绘缺氧特征的全面图景可能有助于我们解释免疫逃逸的潜在机制，并为针对BLCA的缺氧修饰和免疫检查点靶向免疫治疗的临床应用提供启示。
