{"id":"doi:10.1016/j.celrep.2021.109844","kind":"article","title":"Targeting TREM2 on tumor-associated macrophages enhances immunotherapy","authors":["Binnewies M","Pollack JL","Rudolph J","Dash S","Abushawish M","Lee T","Jahchan NS","Canaday P","Lu E","Norng M","Mankikar S","Liu VM","Du X","Chen A","Mehta R","Palmer R","Juric V","Liang L","Baker KP","Reyno L","Krummel MF","Streuli M","Sriram V"],"author_count":23,"year":2021,"published":"2021-10-01","venue":"Cell reports","cited_by":326,"doi":"10.1016/j.celrep.2021.109844","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.celrep.2021.109844","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.celrep.2021.109844","updated":null,"pmid":"34686340","pmcid":null,"openalex_id":null,"pdf_url":null,"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_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"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.","topics":[{"slug":"cancer-immunotherapy","name":"Cancer Immunotherapy","domain_slug":"medicine"}],"cited_in_dossiers":[]}