Increased glycolysis correlates with elevated immune activity in tumor immune microenvironment

作者：Zehang Jiang, Zhixian Liu, Mengyuan Li, Chen Cai, Xiaosheng Wang · 发表于：EBioMedicine · 年份：2019 · DOI：10.1016/j.ebiom.2019.03.068 · 被引用次数：197 · 研究领域：Cancer, Hypoxia, and Metabolism、Ferroptosis and cancer prognosis、Cancer Immunotherapy and Biomarkers

BACKGROUND: Prior studies showed that tumor glycolysis and tumor immune evasion are interdependent. However, a systematic investigation of the association between tumor glycolysis and tumor immunity in various cancers remains lacking. METHODS: Using the Cancer Genome Atlas (TCGA) datasets, we explored the association between glycolytic activity and immune signatures in 14 cancer types. We also explored the associations between glycolytic activity and tumor immunity associated genetic features, including PD-L1 expression, tumor mutation burden (TMB), and tumor aneuploidy. Moreover, we performed in vitro experiments to verify some findings from bioinformatics analysis. Furthermore, we explored the association between tumor glycolytic activity and immunotherapy response. FINDINGS: Glycolytic activity was likely correlated with active immune signatures in various cancers and highly glycolytic tumors presented an immune-stimulatory tumor microenvironment. Compared to TMB and aneuploidy, glycolytic activity was a stronger and more consistent predictor for immune signatures in diverse cancers. Both computational and experimental analyses showed that glycolysis could increase PD-L1 expression in tumor. Glycolytic activity had a strong correlation with apoptosis which was a strong positive predictor for immune signatures, suggesting that apoptosis could be an important medium connecting glycolytic activity with immune activity in cancer. Finally, highly glycolytic tumors exhibited a b...