Metabolic substrates in the tumor microenvironment interacting with transporters and metabolic machinery of TILs (TME-TIL Metabolic Axis)

This target entry describes the complex metabolic interplay between tumor cells and tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment (TME). Tumor cells typically exhibit accelerated glycolysis (the Warburg effect), which depletes essential substrates like glucose and glutamine while promoting the accumulation of immunosuppressive byproducts such as lactate, kynurenine, and adenosine (Leone & Powell, 2020, Nature Reviews Cancer). This nutrient-deprived and toxic environment forces TILs into a state of metabolic exhaustion, characterized by impaired mitochondrial respiration and reduced glycolytic flux, both of which are necessary for robust anti-tumor effector functions (Chang et al., 2015, Cell). Key molecular mediators of this interaction include nutrient transporters such as GLUT1 (SLC2A1) and MCT1/4 (SLC16A1/3), as well as metabolic enzymes like IDO1 and arginase (Xia et al., 2021, Molecular Cancer). Therapeutic strategies targeting these metabolic checkpoints aim to reprogram the TME to favor TIL survival and activity, often as a synergistic approach with immune checkpoint inhibitors.

Other names

Tumor-immune metabolic competitionTME metabolic landscapeTIL metabolic reprogrammingMetabolic checkpoints in cancer immunotherapy

Modulation of nutrient availability and metabolite transport to alleviate metabolic exhaustion and restore effector function in tumor-infiltrating lymphocytes.