Exploring the Impact of TREM2 in Tumor-Associated Macrophages

SIMPLE SUMMARY: TREM2(+) macrophages were recently reported to be highly enriched and associated with immunosuppression in various cancer types. Hence, TREM2 targeting represents a new promising approach for cancer treatment that is based on reprogramming of tumor-associated macrophages to reshape anti-tumor immunity and overcome resistance to current therapies. ABSTRACT: 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.