Lipid metabolism and tumor immunotherapy

Abstract

In recent years, the relationship between lipid metabolism and tumour immunotherapy has been thoroughly investigated. An increasing number of studies have shown that abnormal gene expression and ectopic levels of metabolites related to fatty acid synthesis or fatty acid oxidation affect tumour metastasis, recurrence, and drug resistance. Tumour immunotherapy that aims to promote an antitumour immune response has greatly improved the outcomes for tumour patients. However, lipid metabolism reprogramming in tumour cells or tumour microenvironment-infiltrating immune cells can influence the antitumour response of immune cells and induce tumor cell immune evasion. The recent increase in the prevalence of obesity-related cancers has drawn attention to the fact that obesity increases fatty acid oxidation in cancer cells and suppresses the activation of immune cells, thereby weakening antitumour immunity. This article reviews the changes in lipid metabolism in cells in the tumour microenvironment and describes the relationship between lipid metabolism reprogramming in multiple cell types and tumour immunotherapy.

Keywords: combination therapy; immune cells; immunotherapy; lipid metabolism; tumor microenvironment.

FIGURE 1

The effect of lipid metabolism on a tumor. Factors such as oncogenes and tumor suppressors drive changes in lipid metabolism, and the phospholipids produced by lipid metabolism constitute the cell membrane of tumor cells. Key transcription factors that regulate metabolisms, such as SREBPs (sterol-regulatory element binding proteins), LXRs (liver X-activated receptors), and PPARs (peroxisome proliferators-activated receptors), regulate the proliferation and growth of tumor cells. Adipocytokines (Leptin and Adiponectin) promote tumor angiogenesis. Lipid droplets can provide lipids for tumor cells under extreme conditions. FAO provides energy for tumor cell migration.