Role of FABP5 in T Cell Lipid Metabolism and Function in the Tumor Microenvironment

SIMPLE SUMMARY: T cells infiltrating in the tumor microenvironment play a critical role in anti-tumor immunity. A well-balanced metabolism in T cells determine their function and fate. In this review, we summarize an emerging role of fatty acid binding protein 5 (FABP5, also known as epidermal FABP, or E-FABP), a cytosolic lipid chaperone, in facilitating fatty acid uptake, transport, and metabolism and regulating the differentiation and function of different T cell subsets. Therefore, FABP5 represents a new lipid sensor in determine T cell lipid metabolism and function in the tumor microenvironment. ABSTRACT: To evade immune surveillance, tumors develop a hostile microenvironment that inhibits anti-tumor immunity. Recent immunotherapy breakthroughs that target the reinvigoration of tumor-infiltrating T lymphocytes (TIL) have led to unprecedented success in treating some cancers that are resistant to conventional therapy, suggesting that T cells play a pivotal role in anti-tumor immunity. In the hostile tumor microenvironment (TME), activated T cells are known to mainly rely on aerobic glycolysis to facilitate their proliferation and anti-tumor function. However, TILs usually exhibit an exhausted phenotype and impaired anti-tumor activity due to the limited availability of key nutrients (e.g., glucose) in the TME. Given that different T cell subsets have unique metabolic pathways which determine their effector function, this review introduces our current understanding of T cell development, activation signals and metabolic pathways. Moreover, emerging evidence suggests that fatty acid binding protein 5 (FABP5) expression in T cells regulates T cell lipid metabolism and function. We highlight how FABP5 regulates fatty acid uptake and oxidation, thus shaping the survival and function of different T cell subsets in the TME.