New insights into energy metabolism and immune dynamics could transform head and neck cancer treatment

2025-09-05

(Press-News.org)

Head and neck cancer remains a major global health challenge, ranking among the six most common cancers worldwide and claiming hundreds of thousands of lives each year. A growing body of evidence now points to an intricate connection between energy metabolism and immune regulation as a driving force behind the onset, progression, and treatment resistance of these cancers. The latest comprehensive review on this topic underscores the potential of targeting these intertwined processes to unlock more effective therapies.

Tumor cells in head and neck cancer exhibit profound metabolic reprogramming, altering the way they process glucose, lipids, and amino acids. This reprogramming fuels rapid growth, supports invasion into surrounding tissues, and fortifies tumors against hostile conditions. Changes in glucose transporters and key enzymes accelerate glycolysis, creating a microenvironment rich in lactate that fosters tumor progression and suppresses immune activity. Altered lipid metabolism not only sustains cell membrane production and energy storage but also promotes immune evasion by influencing macrophage polarization and dampening anti-tumor responses. Similarly, restructured amino acid metabolism, particularly in glutamine and arginine pathways, plays a critical role in both tumor growth and the regulation of immune cell activity.

The immune system, a natural line of defense, is often undermined in head and neck cancer. Tumor-driven metabolic shifts deprive CD8⁺ T cells and other immune cells of essential nutrients, weakening their ability to attack malignant cells. At the same time, immune checkpoints such as PD-L1 are upregulated, blocking immune activation. Dysregulation of antigen presentation pathways, altered cytokine signaling, and the recruitment of suppressive immune cells further deepen the immunosuppressive environment.

Importantly, the review highlights that this metabolism–immunity interplay is not just a byproduct of disease—it is a potential therapeutic target. Modulating glucose metabolism through transporter and enzyme inhibitors, interfering with lipid synthesis and cholesterol regulation, or restricting tumor access to key amino acids may tip the balance back in favor of the immune system. Moreover, combining metabolic interventions with immunotherapy could counteract immune suppression and improve patient outcomes, especially in cases resistant to standard treatments.

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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.

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Reference

Haofan Li, Qiu Peng, Linda Oyang, Wenjuan Yang, Shizhen Li, Yaqian Han, Mingjing Peng, Shiming Tan, Longzheng Xia, Jinguan Lin, Xuemeng Xu, Nayiyuan Wu, Yanyan Tang, Xia Luo, Xianjie Jiang, Qianjin Liao, Yujuan Zhou, The regulatory role and mechanism of energy metabolism and immune response in head and neck cancer, Genes & Diseases, Volume 12, Issue 6, 2025, 101607, https://doi.org/10.1016/j.gendis.2025.101607

Funding Information:

National Natural Science Foundation of China 82302987

National Natural Science Foundation of China 82303534

National Natural Science Foundation of China 82203233

National Natural Science Foundation of China 82202966

National Natural Science Foundation of China 82173142

Natural Science Foundation of Hunan Province, China 2023JJ60469

Natural Science Foundation of Hunan Province, China 2023JJ40413

Natural Science Foundation of Hunan Province, China 2023JJ30372

Natural Science Foundation of Hunan Province, China 2023JJ30375

Natural Science Foundation of Hunan Province, China 2023JJ40417

Natural Science Foundation of Hunan Province, China 2020JJ5336

Research Project of Health Commission of Hunan Province, China Z2023086

Research Project of Health Commission of Hunan Province, China R2023093

Research Project of Health Commission of Hunan Province, China R2023040

Research Project of Health Commission of Hunan Province, China 202203034978

Research Project of Health Commission of Hunan Province, China 202202055318

Research Project of Health Commission of Hunan Province, China 202203231032

Research Project of Health Commission of Hunan Province, China 202109031837

Research Project of Health Commission of Hunan Province, China 202109032010

Research Project of Health Commission of Hunan Province, China 20201020

Science and Technology Innovation Program of Hunan Province, China 2023ZJ1122

Science and Technology Innovation Program of Hunan Province, China 2023RC3199

Science and Technology Innovation Program of Hunan Province, China 2023SK4034

Science and Technology Innovation Program of Hunan Province, China 2023RC1073

Science and Technology Innovation Program of Hunan Province, China 2022SK2051

Hunan Provincial Science and Technology Department of China 2020TP1018

Changsha Science and Technology Board of China kh2201054

Ascend Foundation of National Cancer Center (China) NCC201909B06

Hunan Cancer Hospital Climb Plan (China) ZX2020001-3

Hunan Cancer Hospital Climb Plan (China) YF2020002

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New insights into energy metabolism and immune dynamics could transform head and neck cancer treatment

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