Conserved angio-immune subtypes of the cancer microenvironment predict response to immune checkpoint blockade therapy

Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment. However, only a fraction of the patients respond to ICB therapy. Accurate prediction of patients to likely respond to ICB would maximize the efficacy of ICB therapy. The tumor microenvironment (TME) dictates tumor progression and therapy outcome. Here, we classify the TME by analyzing the transcriptome from 11,069 cancer patients based on angiogenesis and T-cell activity. We find three distinct angio-immune TME subtypes conserved across 30 non-hematological cancers. There is a clear inverse relationship between angiogenesis and anti-tumor immunity in TME. Remarkably, patients displaying TME with low angiogenesis with strong anti-tumor immunity show the most significant responses to ICB therapy in four cancers. Re-evaluation of the renal cell carcinoma clinical trials provides compelling evidence that the baseline angio-immune state is robustly predictive of ICB responses. This study offers a rationale for incorporating baseline angio-immune scores for future ICB treatment strategies.

Methods
Data files are derived from processing as derived from manuscript. Code to generate angio-immune clusters is provided.

免疫检查点阻断（Immune checkpoint blockade, ICB）疗法已彻底革新了癌症治疗范式。然而，仅少数患者可从ICB治疗中获益。精准预测哪些患者有望对ICB产生应答，可最大化该疗法的临床效能。肿瘤微环境（tumor microenvironment, TME）决定肿瘤进展与治疗转归。本研究基于血管生成与T细胞活性，对11069名癌症患者的转录组数据进行分析以分型肿瘤微环境，最终在30种非血液系统恶性肿瘤中鉴定出三类保守存在的血管免疫型肿瘤微环境亚型。研究发现，肿瘤微环境中血管生成水平与抗肿瘤免疫活性呈显著负相关。值得注意的是，在四类癌症中，呈现低血管生成水平且抗肿瘤免疫活性较强的肿瘤微环境亚型的患者，对ICB疗法的应答效果最为显著。对肾细胞癌临床试验的重新评估亦提供了确凿证据，表明基线血管免疫状态可稳定预测ICB治疗应答。本研究为未来将基线血管免疫评分纳入ICB治疗策略提供了理论依据。

方法
本研究所用数据文件均源自已发表论文的处理结果。用于生成血管免疫分型簇的代码已公开提供。