Targeting TREM2 on tumor-associated macrophages enhances immunotherapy

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.

Automated summary

Research has identified a correlation between TREM2(+) tumor-associated macrophages (TAMs) and exhausted CD8(+) tumor-infiltrating lymphocytes (TILs), with therapy targeting TREM2 showing potential in promoting anti-tumor immunity.