The interplay between lipid metabolism, cancer progression and anti-cancer immunity

Abstract

The tumour microenvironment (TME) consists of a complex ecosystem of tumour cells, stromal elements, extracellular matrix, fibroblasts and diverse immune-cell populations. Although traditional cancer therapies have primarily focused on eliminating tumour cells, subsequent advances highlighted the importance of modulating immune cells within the TME to enhance anti-tumour immunity. More recently, a major conceptual shift has emerged: targeting nutrient metabolism as a therapeutic strategy. Because tumours create a hypoglycaemic, metabolically restrictive niche, both cancer cells and infiltrating immune cells increasingly rely on lipid uptake, storage and catabolism to sustain their survival and function. This metabolic dependency reveals new vulnerabilities that can be exploited for cancer therapy. In this review, we integrate fundamental concepts of lipid metabolism with recent mechanistic discoveries that define how lipids shape cellular behaviours within the TME, emphasizing the dual roles of lipids as both metabolic substrates and signalling mediators. We also highlight emerging evidence demonstrating that dietary lipid composition — beyond total fat intake — profoundly influences tumour progression and anti-tumour immunity. Together, these insights position lipid metabolism as a critical regulator of tumour biology and an attractive target for next-generation cancer therapies. Lipid metabolism plays a crucial role in cancer progression. This review explores how cancer cells adapt their lipid metabolism to thrive in nutrient-deprived environments, enhancing fatty-acid oxidation and lipid synthesis to support rapid proliferation. The authors discuss the impact of dietary fatty acids on tumour progression, highlighting how specific fats can modulate anti-tumour immunity. They utilize a comprehensive analysis of lipid metabolic pathways, focusing on enzymes such as fatty acid synthase and carnitine palmitoyltransferase 1, which are upregulated in various cancers. The review reveals that targeting these pathways can inhibit tumour growth, as demonstrated by the effectiveness of fatty-acid synthase inhibitors in preclinical models. The study underscores the potential of dietary interventions and metabolic therapies in cancer treatment, suggesting that future research should focus on the interplay between diet, lipid metabolism and cancer to develop effective therapeutic strategies. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.