Solute Carrier transporters in tumor metabolism and immune modulation: implications for therapy

Metabolic reprogramming is a core hallmark of cancer, enabling tumor progression, immune evasion, and therapy resistance. Solute carrier (SLC) transporters, which govern the cellular flux of all nutrients and metabolites, are increasingly recognized as critical drivers of this pathological reprogramming. The altered expression and activity of SLCs in both tumor cells and immune cells profoundly shape the tumor microenvironment (TME) and are directly implicated in clinical outcomes. This review critically examines the roles of key SLC families, particularly those transporting glucose, amino acids, and lipids. We elucidate their dual function in fueling oncogenic proliferation while simultaneously dictating the metabolic competition that leads to the functional suppression of immune cells, including T cells, dendritic cells, and macrophages. We further explore the emerging therapeutic landscape, evaluating strategies that either inhibit SLCs to starve tumors or leverage them to enhance drug delivery and mitigate treatment-related toxicities. Targeting SLC-mediated metabolic pathways represents a novel and highly promising therapeutic axis in oncology. We conclude by outlining the key translational challenges and future opportunities for SLC-targeted strategies. These approaches hold the potential to overcome immunotherapy resistance, reprogram the immunosuppressive TME, and exploit fundamental metabolic dependencies to improve patient outcomes.