ArticleBMC cancer2022
High tumor hexokinase-2 expression promotes a pro-tumorigenic immune microenvironment by modulating CD8+/regulatory T-cell infiltration.
Article in BMC cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Integrated transcriptomic and metabolomic analyses reveal targeting hexokinase 2 disrupts glycolysis and nucleotide metabolism to inhibit NSCLC growth.World journal of surgical oncology · 2026Article
- Ferroptosis-driven metabolic reprogramming in macrophages: Reshaping glucose utilization landscapes.Chinese medical journal · 2026Review
- NAT10 and ac4C modification in cancer immunity and metabolism: emerging mechanisms and therapeutic potential.Journal of translational medicine · 2026Review
- The moonlighting functions of glycolytic enzymes in tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Demethoxycurcumin suppresses HK2-mediated glycolysis by targeting PTEN/Akt signaling.Cancer gene therapy · 2025Article
- Metabolic alterations driven by LDHA in CD8 + T cells promote immune evasion and therapy resistance in NSCLC.Scientific reports · 2025Article
- Graphene Nanocomposites in the Targeting Tumor Microenvironment: Recent Advances in TME Reprogramming.International journal of molecular sciences · 2025Review
- Treatment of Advanced NSCLC Patients with an Anti-Idiotypic NeuGcGM3-Based Vaccine: Immune Correlates in Long-Term Survivors.Biomedicines · 2025Article
- Targeting tumor metabolism to augment CD8Journal of pharmaceutical analysis · 2025Review
- [High expression of hexokinase 2 promotes proliferation, migration and invasion of colorectal cancer cells by activating the JAK/STAT pathway and regulating tumor immune microenvironment].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Hexokinase 2 promotes tumor development and progression.American journal of cancer research · 2025Review
- Microwave ablation triggers OX40L-mediated disruption of TNFRSF4+ Treg immunosuppressive activity.Frontiers in immunology · 2025Article
- Natural products as metabolic modulators to enhance cancer immunotherapy: reprogramming the tumor microenvironment.Frontiers in immunology · 2025Review
- DSCC1 interacts with HSP90AB1 and promotes the progression of lung adenocarcinoma via regulating ER stress.Cancer cell international · 2023Article
- Effects of altered glycolysis levels on CD8Cell death & disease · 2023Review
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRelationship between cancer cell glycolysis and the landscape of tumor immune microenvironment in human cancers was investigated.
methodsForty-one fresh lung adenocarcinoma (ADC) tissues were analyzed using flow cytometry for comprehensive immunoprofiling. Formalin-fixed tissues were immunostained for hexokinase-2 (HK2) to assess cancer cell glycolysis. For validation, formalin-fixed tissues from 375 lung ADC, 118 lung squamous cell carcinoma (SqCC), 338 colon ADC, and 78 lung cancer patients treated with anti-PD-1/PD-L1 immunotherapy were immunostained for HK2, CD8, and FOXP3.
resultsBased on immunoprofiling of lung ADC, HK2 tumor expression was associated with the composition of lymphoid cells rather than myeloid cells. High HK2 tumor expression was associated with immunosuppressive/pro-tumorigenic features, especially decreased ratio of CD8 + T-cells to Tregs (rho = -0.415, P = 0.012). This correlation was also confirmed in four different cohorts including lung ADC and SqCC, colon ADC, and the immunotherapy cohort (rho = -0.175~-0.335, all P < 0.05). A low CD8 + T-cell to Treg ratio was associated with poor progression-free survival and overall survival in lung SqCC patients, and a shorter overall survival in the immunotherapy cohort (all, P < 0.05).
conclusionAn increase in HK2 expression may contribute to shaping the immunosuppressive/pro-tumorigenic tumor microenvironment by modulating the CD8 + T-cell to Treg ratio. Targeting tumor HK2 expression might be a potential strategy for enhancing anti-tumor immunity.
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