通过靶向PD-1/PD-L1或CTLA-4的免疫检查点抑制剂（ICIs）显着改善了癌症患者的预后。然而,大多数实体瘤患者不能从这种治疗中获益。鉴定新的生物标志物以预测ICI的反应对于增强其治疗功效至关重要。TNFR2由CD4+Foxp3+调节性T细胞（Tregs）的最大免疫抑制亚群高度表达，特别是那些存在于肿瘤微环境（TME）。由于Tregs代表了肿瘤免疫逃避的主要细胞机制，TNFR2可能是预测对ICIs治疗的反应的有用生物标志物。我们从泛癌症数据库的已发布的单细胞RNA-seq数据中对计算肿瘤免疫功能障碍和排除（TIDE）框架的分析支持了这一观点。结果表明,正如预期的那样，TNFR2由肿瘤浸润性Treg高度表达。有趣的是,TNFR2在乳腺癌（BRCA）中也由耗尽的CD8T细胞表达，肝细胞癌（HCC），肺鳞状细胞癌（LUSC），和黑色素瘤（MELA）。重要的是,TNFR2的高表达与BRCA对ICIs治疗的反应差有关，HCC,LUSC,还有MELA.总之,TNFR2在TME中的表达可能是ICIs精确治疗癌症患者的可靠生物标志物，这个想法值得进一步研究。
Immune checkpoint inhibitors (ICIs) by targeting PD-1/PD-L1 or CTLA-4 have markedly improved the outcome of cancer patients. However, most solid tumor patients can\'t benefit from such therapy. Identification of novel biomarkers to predict the responses of ICIs is crucial to enhance their therapeutic efficacy. TNFR2 is highly expressed by the maximally immunosuppressive subset of CD4+Foxp3+ regulatory T cells (Tregs), especially those present in tumor microenvironment (TME). Since Tregs represent a major cellular mechanism in tumor immune evasion, TNFR2 may be a useful biomarker to predict the responses to ICIs therapy. This notion is supported by our analysis of the computational tumor immune dysfunction and exclusion (TIDE) framework from published single-cell RNA-seq data of pan-cancer databases. The results show that, as expected, TNFR2 is highly expressed by tumor-infiltrating Tregs. Interestingly, TNFR2 is also expressed by the exhausted CD8 T cells in breast cancer (BRCA), hepatocellular carcinoma (HCC), lung squamous cell carcinoma (LUSC), and melanoma (MELA). Importantly, high expression of TNFR2 is associated with poor responses to the treatment with ICIs in BRCA, HCC, LUSC, and MELA. In conclusion, the expression of TNFR2 in TME may be a reliable biomarker for the precision of ICIs treatment of cancer patients, and this idea merits further research.
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