Galectins at the crossroads of tumor immunity, metabolism, and metastasis: mechanisms, therapeutic resistance, and translational opportunities

作者：Jin C, Wang W, Gao Y · 发表于：Frontiers in immunology · 年份：2026 · DOI：10.3389/fimmu.2026.1849406 · 被引用次数：204 · 研究领域：Galectins、Neoplasms、Humans、Animals、Neoplasm Metastasis、Drug Resistance, Neoplasm、Signal Transduction、Tumor Microenvironment、Metabolic Reprogramming

Galectins, a structurally conserved family of β-galactoside-binding lectins, have emerged as key regulators of cancer progression. However, their integrated roles across tumor immunity, metabolic rewiring, and metastasis have yet to be fully defined. In this review, we synthesize current evidence on major galectin family members, particularly galectin (Gal)-1, Gal-3, Gal-4, Gal-7, Gal-9, and Gal-13, and delineate how they drive tumor progression through mechanistically distinct yet convergent pathways. Specifically, galectins induce T-cell dysfunction through T-cell immunoglobulin and mucin-domain containing-3 (TIM-3)- and programmed cell death protein 1 (PD-1)-associated signaling, reprogram macrophages and myeloid-derived suppressor cells (MDSCs) via phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), Janus kinase/signal transducer and activator of transcription (JAK/STAT), and nuclear factor kappa B (NF-κB) pathways, and modulate innate immune effectors, including natural killer (NK) cells, neutrophils, and dendritic cells, in a context-dependent manner. Beyond immune regulation, galectins reshape tumor metabolism through effects on glycolysis, lipid metabolism, and glycan remodeling, and differentially regulate ferroptosis susceptibility, with the contrasting roles of Gal-1 and Gal-13 underscoring functional diversity within the family. Emerging evidence further implicates galectins in resistance to chemotherapy, targeted therapy, immune checkpoint blockade, and chimer...