Immunometabolism of T cells and macrophages: Human translational perspectives

Immunometabolism explores how immune-cell function depends on cellular energy metabolism. Recent insights demonstrate that nutrient utilization dictates activation, polarization, and tolerance.

To systematically review human studies on T-cell and macrophage metabolism, identify converging pathways, and outline translational implications for inflammation, autoimmunity, and cancer.

Following PRISMA 2020 guidelines, PubMed was searched (2015-2025) using predefined MeSH terms ("immunometabolism", "T lymphocytes", "macrophages", "metabolic reprogramming"). Of 999 records, 67 met inclusion criteria (human data, peer-reviewed, quantitative endpoints). Bias was assessed with ROBIS.

Effector T cells and M1 macrophages favor glycolysis for rapid ATP and pro-inflammatory signaling, whereas memory T cells and M2 macrophages rely on oxidative phosphorylation and fatty-acid oxidation for sustained energy and tolerance. mTORC1/AMPK signaling, glutaminolysis, and the kynurenine pathway integrate metabolic and immune cues. Metabolic dysregulation in obesity or tumor microenvironments skews these pathways, driving chronic inflammation or immune escape.

Human immunometabolism is defined by dynamic substrate switching. Targeting glycolysis, FAO, or tryptophan metabolism offers therapeutic leverage in cancer and autoimmune disease. Future directions include single-cell and spatial metabolomics and integrative metabolic-immune modeling.