Targeting TREM2 on tumor-associated macrophages enhances immunotherapy

Abstract

Converting checkpoint inhibitor (CPI)-resistant individuals to being responsive requires identifying suppressive mechanisms. We identify TREM2 + tumor-associated macrophages (TAMs) as being correlated with exhausted CD8 + tumor-infiltrating lymphocytes (TILs) in mouse syngeneic tumor models and human solid tumors of multiple histological types. Fc domain-enhanced anti-TREM2 monoclonal antibody (mAb) therapy promotes anti-tumor immunity by elimination and modulation of TAM populations, which leads to enhanced CD8 + TIL infiltration and effector function. TREM2 + TAMs are most enriched in individuals with ovarian cancer, where TREM2 expression corresponds to disease grade accompanied by worse recurrence-free survival. In an aggressive orthotopic ovarian cancer model, anti-TREM2 mAb therapy drives potent anti-tumor immunity. These results highlight TREM2 as a highly attractive target for immunotherapy modulation in individuals who are refractory to CPI therapy and likely have a TAM-rich tumor microenvironment.

Abstract of "Targeting TREM2 on tumor-associated macrophages enhances immunotherapy" by Binnewies M, Pollack JL, Rudolph J et al., https://doi.org/10.1016/j.celrep.2021.109844, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.