Exploring the Impact of TREM2 in Tumor-Associated Macrophages.

Tumor-associated macrophages (TAMs) represent a key component of the tumor microenvironment and are generally associated with immunosuppression and poor prognosis. TREM2 is a transmembrane receptor of the immunoglobulin superfamily expressed in myeloid cells. TREM2 has been extensively studied in microglia and neurodegenerative diseases and recently emerged as a marker of pro-tumorigenic macrophages. The accumulation of TREM2-expressing TAMs was reported across numerous cancer patients and tumor models. TREM2 genetic blockade or TREM2 targeting with antibodies resulted in improved tumor control, enhanced response to anti-PD1, and significant changes in the tumor immune landscape. Preclinical studies paved the way for an ongoing clinical trial with a TREM2 depleting antibody and inspired further exploration of TREM2 targeting therapies. Here, we review the current knowledge about the impact of TREM2 in cancer, with an emphasis on the TREM2 macrophage signature across different cancer types, the contribution of TREM2 to TAM phenotype and function, and the promising effects of TREM2 modulation.