Journal article
Macrophage-Targeted Therapy Unlocks Antitumoral Cross-talk between IFNγ-Secreting Lymphocytes and IL12-Producing Dendritic Cells
Cancer immunology research, v 10(1), pp 40-55
Jan 2022
PMID: 34795032
Featured in Collection : UN Sustainable Development Goals @ Drexel
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
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.
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Details
- Title
- Macrophage-Targeted Therapy Unlocks Antitumoral Cross-talk between IFNγ-Secreting Lymphocytes and IL12-Producing Dendritic Cells
- Creators
- Christina Pfirschke - Center for Systems BiologyRapolas Zilionis - Harvard Medical SchoolCamilla Engblom - Center for Systems BiologyMarius Messemaker - Center for Systems BiologyAngela E Zou - Center for Systems BiologySteffen Rickelt - Massachusetts Institute of TechnologyNicolas A Gort-Freitas - Harvard Medical SchoolYunkang Lin - Center for Systems BiologyRuben Bill - Center for Systems BiologyMarie Siwicki - Center for Systems BiologyJeremy Gungabeesoon - Center for Systems BiologyMelissa M Sprachman - Center for Systems BiologyAngela N Marquard - Center for Systems BiologyChristopher B Rodell - Center for Systems BiologyMichael F Cuccarese - Center for Systems BiologyJeremy Quintana - Center for Systems BiologyMaaz S Ahmed - Center for Systems BiologyRainer H Kohler - Center for Systems BiologyVirginia Savova - Harvard Medical SchoolRalph Weissleder - Center for Systems BiologyAllon M Klein - Harvard UniversityMikael J Pittet - Center for Systems Biology
- Publication Details
- Cancer immunology research, v 10(1), pp 40-55
- Publisher
- American Association for Cancer Research (AACR)
- Grant note
- U01 CA206997 / NCI NIH HHS R33 CA202064 / NCI NIH HHS R01 CA218579 / NCI NIH HHS R01 AI084880 / NIAID NIH HHS R01 AI123349 / NIAID NIH HHS R01 CA206890 / NCI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000741482900001
- Scopus ID
- 2-s2.0-85122965983
- Other Identifier
- 991019320714704721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology
- Oncology