Only a subset of patients treated with immune checkpoint inhibitors (CPIs) respond to the treatment, and distinguishing responders from non-responders is a major challenge. Many proposed biomarkers of CPI response and survival probably represent alternative measurements of the same aspects of the tumor, its microenvironment or the host. Thus, we currently ignore how many truly independent biomarkers there are. With an unbiased analysis of genomics, transcriptomics and clinical data of a cohort of patients with metastatic tumors (n = 479), we discovered five orthogonal latent factors: tumor mutation burden, T cell effective infiltration, transforming growth factor-beta activity in the microenvironment, prior treatment and tumor proliferative potential. Their association with CPI response and survival was observed across all tumor types and validated across six independent cohorts (n = 1,491). These five latent factors constitute a frame of reference to organize current and future knowledge on biomarkers of CPI response and survival.

只有一小部分接受免疫检查点抑制剂（CPI）治疗的患者对治疗有反应，区分反应者和无反应者是一个重大挑战。许多提出的 CPI 反应和生存的生物标志物可能代表了肿瘤、其微环境或宿主的相同方面的替代测量。因此，我们目前忽略了有多少真正独立的生物标志物。通过对一组转移性肿瘤患者 ( n = 479) 的基因组学、转录组学和临床数据进行公正分析，我们发现了五个正交潜在因素：肿瘤突变负荷、T 细胞有效浸润、微环境中的转化生长因子-β 活性、既往治疗和肿瘤增殖潜力。在所有肿瘤类型中观察到它们与 CPI 反应和生存的关联，并在六个独立队列中进行验证 ( n = 1,491)。这五个潜在因素构成了一个参考框架，用于组织当前和未来有关 CPI 反应和生存的生物标志物的知识。