| Autor: |
Mikhail Binnewies, Joshua L. Pollack, Joshua Rudolph, Subhadra Dash, Marwan Abushawish, Tian Lee, Nadine S. Jahchan, Pamela Canaday, Erick Lu, Manith Norng, Shilpa Mankikar, Victoria M. Liu, Xiaoyan Du, Amanda Chen, Ranna Mehta, Rachael Palmer, Vladislava Juric, Linda Liang, Kevin P. Baker, Leonard Reyno, Matthew F. Krummel, Michel Streuli, Venkataraman Sriram |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Cell Reports, Vol 37, Iss 3, Pp 109844- (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2021.109844 |
| Popis: |
Summary: 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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