TREM2-mediated regulation of myeloid cells in the tumor microenvironment: new insights and therapeutic prospects
Yueyu Huang, Wanxia Fang
Abstract
Triggering receptor expressed on myeloid cells 2 (TREM2) has recently been identified as a key regulator of myeloid cell function within the tumor microenvironment (TME). Accumulating evidence indicates that TREM2-expressing tumor-associated macrophages and myeloid-derived suppressor cells promote immunosuppression, tumor progression, and resistance to immunotherapy. Through modulation of cellular metabolism, antigen presentation, and cytokine secretion, TREM2 signaling critically shapes tumor immune dynamics. Owing to this central role, TREM2 has emerged as a promising immunotherapeutic target. Preclinical and clinical studies demonstrate that TREM2 blockade can reprogram the immunosuppressive TME, enhance T-cell infiltration, and augment the efficacy of immune checkpoint inhibitors. This review synthesizes current knowledge of the molecular mechanisms underlying TREM2 signaling in myeloid cells, its influence on TME remodeling, and its potential as both a biomarker and therapeutic target in cancer immunotherapy. Finally, we highlight current challenges and future perspectives in harnessing TREM2-directed strategies to counteract tumor immune evasion.