Immunometabolism of T cells and macrophages: Human translational perspectives

BACKGROUND: Immunometabolism explores how immune-cell function depends on cellular energy metabolism. Recent insights demonstrate that nutrient utilization dictates activation, polarization, and tolerance. AIMS: To systematically review human studies on T-cell and macrophage metabolism, identify converging pathways, and outline translational implications for inflammation, autoimmunity, and cancer. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.