FABPs-mediated lipid signaling pathways in tumor reprogramming: bidirectional crosstalk with the immune microenvironment.

Fatty acid-binding proteins (FABPs) are cytoplasmic lipid chaperones that regulate intracellular fatty acid trafficking and metabolic homeostasis. Increasing evidence identifies FABPs as key drivers of tumor metabolic reprogramming. Within the broader tumor microenvironment (TME), particularly its immune compartment, the tumor immune microenvironment (TIME), FABP isoforms coordinate lipid uptake, synthesis, oxidation, and storage, thereby supporting tumor growth and metastatic progression. Beyond tumor cells, FABP-dependent lipid remodeling shapes immune cell function and tumor-immune crosstalk by modulating lipid availability and redox balance. Conversely, tumor-microenvironmental cues, including adipocyte-derived lipids, obesity-associated fatty acids, macrophage polarization signals, and immune-checkpoint signaling, can regulate FABP expression and redistribute lipid metabolic programs among tumor and immune cells. Given their central function in lipid metabolic networks, FABPs represent promising therapeutic targets. Unlike previous FABP4-centered reviews, this review emphasizes multi-isoform FABP-mediated lipid metabolic crosstalk across tumor and immune-cell compartments, highlighting reciprocal TME regulation, immune-cell dysfunction, and therapeutic responsiveness.