Macrophage-Targeted Therapy Unlocks Antitumoral Cross-talk between IFNγ-Secreting Lymphocytes and IL12-Producing Dendritic Cells.
Details
Serval ID
serval:BIB_6C392024C141
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Macrophage-Targeted Therapy Unlocks Antitumoral Cross-talk between IFNγ-Secreting Lymphocytes and IL12-Producing Dendritic Cells.
Journal
Cancer immunology research
ISSN
2326-6074 (Electronic)
ISSN-L
2326-6066
Publication state
Published
Issued date
01/2022
Peer-reviewed
Oui
Volume
10
Number
1
Pages
40-55
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
Publication Status: ppublish
Publication Status: ppublish
Abstract
Macrophages often abound within tumors, express colony-stimulating factor 1 receptor (CSF1R), and are linked to adverse patient survival. Drugs blocking CSF1R signaling have been used to suppress tumor-promoting macrophage responses; however, their mechanisms of action remain incompletely understood. Here, we assessed the lung tumor immune microenvironment in mice treated with BLZ945, a prototypical small-molecule CSF1R inhibitor, using single-cell RNA sequencing and mechanistic validation approaches. We showed that tumor control was not caused by CSF1R <sup>+</sup> cell depletion; instead, CSF1R targeting reshaped the CSF1R <sup>+</sup> cell landscape, which unlocked cross-talk between antitumoral CSF1R <sup>-</sup> cells. These cells included IFNγ-producing natural killer and T cells, and an IL12-producing dendritic cell subset, denoted as DC <sub>3</sub> , which were all necessary for CSF1R inhibitor-mediated lung tumor control. These data indicate that CSF1R targeting can activate a cardinal cross-talk between cells that are not macrophages and that are essential to mediate the effects of T cell-targeted immunotherapies and promote antitumor immunity.See related Spotlight by Burrello and de Visser, p. 4.
Pubmed
Web of science
Create date
21/01/2022 18:42
Last modification date
15/07/2022 6:35