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Neutrophils Driving Unconventional T Cells Mediate Resistance against Murine Sarcomas and Selected Human Tumors
- Source :
- Cell
- Publication Year :
- 2019
-
Abstract
- Summary Neutrophils are a component of the tumor microenvironment and have been predominantly associated with cancer progression. Using a genetic approach complemented by adoptive transfer, we found that neutrophils are essential for resistance against primary 3-methylcholantrene-induced carcinogenesis. Neutrophils were essential for the activation of an interferon-γ-dependent pathway of immune resistance, associated with polarization of a subset of CD4− CD8− unconventional αβ T cells (UTCαβ). Bulk and single-cell RNA sequencing (scRNA-seq) analyses unveiled the innate-like features and diversity of UTCαβ associated with neutrophil-dependent anti-sarcoma immunity. In selected human tumors, including undifferentiated pleomorphic sarcoma, CSF3R expression, a neutrophil signature and neutrophil infiltration were associated with a type 1 immune response and better clinical outcome. Thus, neutrophils driving UTCαβ polarization and type 1 immunity are essential for resistance against murine sarcomas and selected human tumors.<br />Graphical Abstract<br />Highlights • Neutrophils mediate antitumor response by sustaining an IL-12/IFNγ-dependent pathway • Neutrophils are essential for unconventional αβ T cell (UTCαβ) type 1 polarization • Type 1 UTCαβ possess an innate-like phenotype and display antitumor potential in vivo • Neutrophil infiltration is associated with good prognosis in selected human tumors<br />Tumor-associated neutrophils (TANs) have mainly been portrayed as tumor-promoters. Here, we describe a novel antitumor pathway in which TANs promote IL-12 production by macrophages, leading to type 1 polarization of a subset of unconventional αβ T cell (UTCαβ). Type 1 UTCαβ possess an innate-like phenotype and antitumor potential in vivo. In selected human tumors, neutrophil infiltration is associated with type 1 immunity and better clinical outcome.
- Subjects :
- Male
Adoptive cell transfer
Neutrophils
T-Lymphocytes
macrophage
Kaplan-Meier Estimate
Biology
medicine.disease_cause
soft tissue sarcomas
General Biochemistry, Genetics and Molecular Biology
Undifferentiated Pleomorphic Sarcoma
Article
03 medical and health sciences
Interferon-gamma
Mice
0302 clinical medicine
Immune system
Immunity
Neoplasms
Receptors, Colony-Stimulating Factor
medicine
Tumor Microenvironment
Animals
Humans
carcinogenesi
tumor immunology
innate immunity
030304 developmental biology
Disease Resistance
Mice, Knockout
0303 health sciences
Tumor microenvironment
Innate immune system
Macrophages
neutrophil
Sarcoma
unconventional T cells
Interleukin-12
Immunity, Innate
Mice, Inbred C57BL
Neutrophil Infiltration
Chromones
soft tissue sarcoma
Cancer research
Interleukin 12
Carcinogenesis
carcinogenesis
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 10974172
- Volume :
- 178
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.doi.dedup.....1f028d0a60cbdd576b0aa15e085d2182