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
Author(s)
Pfirschke C., Zilionis R., Engblom C., Messemaker M., Zou A.E., Rickelt S., Gort-Freitas N.A., Lin Y., Bill R., Siwicki M., Gungabeesoon J., Sprachman M.M., Marquard A.N., Rodell C.B., Cuccarese M.F., Quintana J., Ahmed M.S., Kohler R.H., Savova V., Weissleder R., Klein A.M., Pittet M.J.
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
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 17:42
Last modification date
15/07/2022 5:35
Usage data