Increased glycolysis correlates with elevated immune activity in tumor immune microenvironment

Area of Science:

• Oncology
• Cancer Immunology
• Metabolic Reprogramming

Background:

• Prior research indicates a link between tumor glycolysis and immune evasion.
• A comprehensive analysis of tumor glycolysis's relationship with tumor immunity across various cancers is needed.

Purpose of the Study:

• To investigate the association between tumor glycolytic activity and immune signatures in 14 cancer types.
• To explore the relationship between glycolytic activity, tumor mutation burden (TMB), tumor aneuploidy, and PD-L1 expression.
• To determine if tumor glycolytic activity can predict immunotherapy response.

Main Methods:

• Utilized The Cancer Genome Atlas (TCGA) datasets for bioinformatics analysis.
• Performed in vitro experiments to validate computational findings.
• Analyzed associations between glycolytic activity, immune signatures, and genetic features like TMB and PD-L1.

Main Results:

• Glycolytic activity positively correlates with active immune signatures and an immune-stimulatory tumor microenvironment.
• Glycolytic activity is a robust predictor of immune signatures, surpassing TMB and aneuploidy.
• Glycolysis increases PD-L1 expression and correlates with apoptosis, a key mediator of immune activity.
• Highly glycolytic tumors show improved immunotherapy response and survival.

Conclusions:

• Tumor glycolysis may enhance anti-PD-1/PD-L1 immunotherapy efficacy by boosting tumor immunity and PD-L1 expression.
• Tumor glycolytic activity serves as a potential predictive biomarker for immunotherapy response in diverse cancers.