Article ; Online: TREM1 activation of myeloid cells promotes antitumor immunity.
Science translational medicine
2023 Volume 15, Issue 711, Page(s) eadd9990
Abstract: Myeloid cells in the tumor microenvironment (TME) can exist in immunosuppressive and immunostimulatory states that impede or promote antitumor immunity, respectively. Blocking suppressive myeloid cells or increasing stimulatory cells to enhance antitumor ...
| Abstract | Myeloid cells in the tumor microenvironment (TME) can exist in immunosuppressive and immunostimulatory states that impede or promote antitumor immunity, respectively. Blocking suppressive myeloid cells or increasing stimulatory cells to enhance antitumor immune responses is an area of interest for therapeutic intervention. Triggering receptor expressed on myeloid cells-1 (TREM1) is a proinflammatory receptor that amplifies immune responses. TREM1 is expressed on neutrophils, subsets of monocytes and tissue macrophages, and suppressive myeloid populations in the TME, including tumor-associated neutrophils, monocytes, and tumor-associated macrophages. Depletion or inhibition of immunosuppressive myeloid cells, or stimulation by TREM1-mediated inflammatory signaling, could be used to promote an immunostimulatory TME. We developed PY159, an afucosylated humanized anti-TREM1 monoclonal antibody with enhanced FcγR binding. PY159 is a TREM1 agonist that induces signaling, leading to up-regulation of costimulatory molecules on monocytes and macrophages, production of proinflammatory cytokines and chemokines, and enhancement of T cell activation in vitro. An antibody against mouse TREM1, PY159m, promoted antitumor efficacy in syngeneic mouse tumor models. These results suggest that PY159-mediated agonism of TREM1 on tumoral myeloid cells can promote a proinflammatory TME and offer a promising strategy for immunotherapy. |
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| MeSH term(s) | Animals ; Mice ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal/therapeutic use ; Disease Models, Animal ; Immunosuppressive Agents ; Macrophages ; Monocytes ; Myeloid Cells ; Triggering Receptor Expressed on Myeloid Cells-1 |
| Chemical Substances | Antibodies, Monoclonal ; Immunosuppressive Agents ; Triggering Receptor Expressed on Myeloid Cells-1 ; TREM1 protein, mouse |
| Language | English |
| Publishing date | 2023-08-30 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2518854-9 |
| ISSN | 1946-6242 ; 1946-6234 |
| ISSN (online) | 1946-6242 |
| ISSN | 1946-6234 |
| DOI | 10.1126/scitranslmed.add9990 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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