| First Author | Pfirschke C | Year | 2022 |
| Journal | Cancer Immunol Res | Volume | 10 |
| Issue | 1 | Pages | 40-55 |
| PubMed ID | 34795032 | Mgi Jnum | J:360194 |
| Mgi Id | MGI:7664678 | Doi | 10.1158/2326-6066.CIR-21-0326 |
| Citation | Pfirschke C, et al. (2022) Macrophage-Targeted Therapy Unlocks Antitumoral Cross-talk between IFNgamma-Secreting Lymphocytes and IL12-Producing Dendritic Cells. Cancer Immunol Res 10(1):40-55 |
| abstractText | 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(+) cell depletion; instead, CSF1R targeting reshaped the CSF1R(+) cell landscape, which unlocked cross-talk between antitumoral CSF1R(-) cells. These cells included IFNgamma-producing natural killer and T cells, and an IL12-producing dendritic cell subset, denoted as DC(3), 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. |
