Solute carrier transporters: emerging central players in tumour immunotherapy

Solute carrier transporters (SLCs) mediate nutrient and metabolite cellular homeostasis. Immune cells depend on SLCs to induce rapid and robust metabolic reprogramming, thereby controlling diverse immunological responses. Recent studies hint toward an important role of SLCs in immunity. Here, we review the emerging roles of SLCs in immunotherapy via modifying the metabolism and effector functions of immune cells. We focus on the roles of three major nutrient (glucose, amino acid, and lipid)-related transporters in immunity of representative cells [T cells, dendritic cells (DCs), natural killer (NK) cells, and macrophages) in innate and adaptive immunity. Other SLCs, such as ion transporters are also briefly discussed. Finally, we propose some potential strategies for targeting SLCs to augment tumour immunotherapy. Nutrient and metabolite transporters in activated immune cells are drastically regulated for rapid metabolic reprogramming.To upregulate specific SLC transporters of immune cells in the tumour microenvironment (TME), while blocking certain SLCs in the tumour cells can augment immunotherapy.Metabolites transported by SLCs not only provide energy sources for immune cells, but also yield precursors for cell biosynthesis or act as signal molecules to participate in signal transduction and gene regulation.Reviewing the roles of SLCs in varied immune cells systematically may pave the way for the future improvement of immunotherapies by manipulating immunometabolism.Jointly targeting and editing SLCs on shared or different immune cells can enhance the existing immunotherapy (e.g., adoptive immunotherapy).