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.