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.

Neutrophils Driving Unconventional T Cells Mediate Resistance against Murine Sarcomas and Selected Human Tumors

Cananzi F;Colombo P;Garlanda C;Mantovani A;Jaillon S
2019

Abstract

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.
carcinogenesis
innate immunity
interleukin-12
macrophages
neutrophils
soft tissue sarcomas
tumor immunology
unconventional T cells
Animals
Chromones
Humans
Immunity, Innate
Interferon-gamma
Interleukin-12
Kaplan-Meier Estimate
Macrophages
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Neoplasms
Neutrophil Infiltration
Neutrophils
Receptors, Colony-Stimulating Factor
Sarcoma
T-Lymphocytes
Tumor Microenvironment
Disease Resistance
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11699/5761
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