Metabolic mechanisms of immunotherapy resistance

Immunotherapy has revolutionized cancer treatment, yet its efficacy is frequently compromised by metabolic mechanisms that drive resistance. Understanding how tumor metabolism shapes the immune microenvironment is essential for developing effective therapeutic strategies. This review examines key me...

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Detalhes bibliográficos
Autores: Cabezón-Guitiérrez, Luis, Cabezón-Gutiérrez, Luis, Palka-Kotlowska, Magda, Custodio-Cabello, Sara, Chacón-Ovejero, Beatriz, Pacheco-Barcia, Vilma
Formato: artículo
Fecha de publicación:2025
País:España
Recursos:Universidad de Málaga
Repositorio:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
Idioma:inglés
OAI Identifier:oai:ddfv.ufv.es:10641/6347
Acesso em linha:https://hdl.handle.net/10641/6347
Access Level:acceso abierto
Palavra-chave:Immune resistance
cancer
metabolism
tumor microenvironment
Oncology
Cancer Research
SDG 3 - Good Health and Well-being
Journal Article
Review
Yes
yes
Descrição
Resumo:Immunotherapy has revolutionized cancer treatment, yet its efficacy is frequently compromised by metabolic mechanisms that drive resistance. Understanding how tumor metabolism shapes the immune microenvironment is essential for developing effective therapeutic strategies. This review examines key metabolic pathways influencing immunotherapy resistance, including glucose, lipid, and amino acid metabolism. We discuss their impact on immune cell function and tumor progression, highlighting emerging therapeutic strategies to counteract these effects. Tumor cells undergo metabolic reprogramming to sustain proliferation, altering the availability of essential nutrients and generating toxic byproducts that impair cytotoxic T lymphocytes (CTLs) and natural killer (NK) cell activity. The accumulation of lactate, deregulated lipid metabolism, and amino acid depletion contribute to an immunosuppressive tumor microenvironment (TME). Targeting metabolic pathways, such as inhibiting glycolysis, modulating lipid metabolism, and restoring amino acid balance, has shown promise in enhancing immunotherapy response. Addressing metabolic barriers is crucial to overcoming immunotherapy resistance. Integrating metabolic-targeted therapies with immune checkpoint inhibitors may improve clinical outcomes. Future research should focus on personalized strategies to optimize metabolic interventions and enhance antitumor immunity.