Fatty acid metabolism of immune cells: a new target of tumour immunotherapy

Abstract

Metabolic competition between tumour cells and immune cells for limited nutrients is an important feature of the tumour microenvironment (TME) and is closely related to the outcome of tumour immune escape. A large number of studies have proven that tumour cells need metabolic reprogramming to cope with acidification and hypoxia in the TME while increasing energy uptake to support their survival. Among them, synthesis, oxidation and uptake of fatty acids (FAs) in the TME are important manifestations of lipid metabolic adaptation. Although different immune cell subsets often show different metabolic characteristics, various immune cell functions are closely related to fatty acids, including providing energy, providing synthetic materials and transmitting signals. In the face of the current situation of poor therapeutic effects of tumour immunotherapy, combined application of targeted immune cell fatty acid metabolism seems to have good therapeutic potential, which is blocked at immune checkpoints. Combined application of adoptive cell therapy and cancer vaccines is reflected. Therefore, it is of great interest to explore the role of fatty acid metabolism in immune cells to discover new strategies for tumour immunotherapy and improve anti-tumour immunity.

Fig. 1. Fatty acid metabolism of tumour cells.

Tumour cells absorb fatty acids by expressing FAT (also known as CD36), FATPs and FABP on the plasma membrane and exosome transport and carry out β-oxidation and the tricarboxylic acid cycle.

Fig. 2. Targets of Fatty Acid Metabolism in immune cells.

Immune cells (CD8⁺T cell, Treg, TAM, DC) in tumor microenvironment regulate the process of fatty acid metabolism through corresponding targets, which in turn affect the function of immune cells and their sensitivity to immunotherapy.

Fig. 3. Factors affecting fatty acid metabolism of immune cells in the tumour microenvironment.

The tumour microenvironment contains a variety of immune cells, and the factors that affect its fatty acid metabolism are described in this review.

Fig. 4. Application of fatty acid metabolism in tumor immunotherapy.

A Immune cells enhance fatty acid metabolism through corresponding targets, thus increasing the efficacy of ICBs. B Some short-chain fatty acids enhanced the efficacy of CD8⁺T cells treated with CAR-T. C Promote the combination of immune cell fatty acid metabolism and tumor vaccine.