Details

Autor(en) / Beteiligte

• Pfirschke, Christina
• Zilionis, Rapolas
• Engblom, Camilla
• Messemaker, Marius
• Zou, Angela E
• Rickelt, Steffen
• Gort-Freitas, Nicolas A
• Lin, Yunkang
• Bill, Ruben
• Siwicki, Marie
• Gungabeesoon, Jeremy
• Sprachman, Melissa M
• Marquard, Angela N
• Rodell, Christopher B
• Cuccarese, Michael F
• Quintana, Jeremy
• Ahmed, Maaz S
• Kohler, Rainer H
• Savova, Virginia
• Weissleder, Ralph
• Klein, Allon M
• Pittet, Mikael J

Titel

Macrophage-Targeted Therapy Unlocks Antitumoral Cross-talk between IFNγ-Secreting Lymphocytes and IL12-Producing Dendritic Cells

Ist Teil von

• Cancer immunology research, 2022-01, Vol.10 (1), p.40-55

Ort / Verlag

United States

Erscheinungsjahr

2022

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 IFNγ-producing natural killer and T cells, and an IL12-producing dendritic cell subset, denoted as DC , 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.