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Immunometabolism in lung cancer - The link between metabolism and immune response.

iScience 2026 Vol.29(3) p. 115041

Eivazzadeh Y, Orooji N, Eskandari T, Tarahomi M, Tavassoli Razavi F, Haghmorad D

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Lung cancer remains a leading cause of cancer-related mortality worldwide, characterized by complex interactions between tumor metabolism and immune evasion mechanisms.

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APA Eivazzadeh Y, Orooji N, et al. (2026). Immunometabolism in lung cancer - The link between metabolism and immune response.. iScience, 29(3), 115041. https://doi.org/10.1016/j.isci.2026.115041
MLA Eivazzadeh Y, et al.. "Immunometabolism in lung cancer - The link between metabolism and immune response.." iScience, vol. 29, no. 3, 2026, pp. 115041.
PMID 41797927

Abstract

Lung cancer remains a leading cause of cancer-related mortality worldwide, characterized by complex interactions between tumor metabolism and immune evasion mechanisms. This review explores the emerging field of immunometabolism, highlighting how metabolic reprogramming within lung tumors not only fuels cancer progression but also shapes the tumor immune microenvironment (TME). Key metabolic pathways, such as glycolysis, glutaminolysis, and lipid metabolism, are extensively altered in lung cancer cells, facilitating immune suppression through mechanisms such as nutrient competition, lactate accumulation, and modulation of immune checkpoints. Immune cells, including tumor-associated macrophages (TAMs), T cells, NK cells, and dendritic cells, undergo functional impairment due to these metabolic constraints. The review further discusses therapeutic strategies targeting immunometabolic pathways, including inhibitors of glucose and amino acid transporters, lipid biosynthesis enzymes, and immune-metabolic checkpoints such as IDO and CD73. Despite promising preclinical outcomes, challenges such as metabolic plasticity, systemic toxicity, and limited biomarker availability hinder clinical translation. Future directions emphasize the integration of multi-omics, metabolic profiling, and combinatory immunotherapy to personalize treatment and overcome resistance. A deeper understanding of immunometabolic crosstalk is pivotal for advancing precision medicine in lung cancer.