Immunometabolism in lung cancer – The link between metabolism and immune response

TL;DR

This review explores how metabolism in lung cancer cells affects immune responses, offering insights into new treatment strategies.

Contribution

The paper provides a comprehensive overview of immunometabolism in lung cancer and potential therapeutic strategies.

Findings

Metabolic reprogramming in lung cancer cells suppresses immune responses through nutrient competition and lactate accumulation.

Therapies targeting immunometabolic pathways show promise but face challenges like toxicity and resistance.

Future approaches involve combining multi-omics and immunotherapy to improve treatment personalization.

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.

Immunology; Cancer

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