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

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5 Citations (Scopus)

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. 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.

Original languageEnglish
Pages (from-to)346-360.e24
JournalCell
Volume178
Issue number2
DOIs
Publication statusPublished - Jul 11 2019

Fingerprint

T-cells
Sarcoma
Tumors
Neutrophils
T-Lymphocytes
Neoplasms
Polarization
Infiltration
Immunity
Neutrophil Infiltration
Macrophages
Interleukin-12
RNA Sequence Analysis
Carcinogens
Interferons
Tumor Microenvironment
Adoptive Transfer
T-Lymphocyte Subsets
Chemical activation
RNA

Keywords

  • carcinogenesis
  • innate immunity
  • interleukin-12
  • macrophages
  • neutrophils
  • soft tissue sarcomas
  • tumor immunology
  • unconventional T cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

@article{25b46d1f1e5b49099151018e17248891,
title = "Neutrophils Driving Unconventional T Cells Mediate Resistance against Murine Sarcomas and Selected Human Tumors",
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. 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.",
keywords = "carcinogenesis, innate immunity, interleukin-12, macrophages, neutrophils, soft tissue sarcomas, tumor immunology, unconventional T cells",
author = "Andrea Ponzetta and Roberta Carriero and Silvia Carnevale and Marialuisa Barbagallo and Martina Molgora and Chiara Perucchini and E. Magrini and Francesca Gianni and P. Kunderfranco and N. Polentarutti and F. Pasqualini and {Di Marco}, Sabrina and Domenico Supino and Clelia Peano and Ferdinando Cananzi and Piergiuseppe Colombo and Silvana Pilotti and Alomar, {Suliman Yousef} and Eduardo Bonavita and Galdiero, {Maria Rosaria} and Cecilia Garlanda and Alberto Mantovani and Sebastien Jaillon",
year = "2019",
month = "7",
day = "11",
doi = "10.1016/j.cell.2019.05.047",
language = "English",
volume = "178",
pages = "346--360.e24",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",

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TY - JOUR

T1 - Neutrophils Driving Unconventional T Cells Mediate Resistance against Murine Sarcomas and Selected Human Tumors

AU - Ponzetta, Andrea

AU - Carriero, Roberta

AU - Carnevale, Silvia

AU - Barbagallo, Marialuisa

AU - Molgora, Martina

AU - Perucchini, Chiara

AU - Magrini, E.

AU - Gianni, Francesca

AU - Kunderfranco, P.

AU - Polentarutti, N.

AU - Pasqualini, F.

AU - Di Marco, Sabrina

AU - Supino, Domenico

AU - Peano, Clelia

AU - Cananzi, Ferdinando

AU - Colombo, Piergiuseppe

AU - Pilotti, Silvana

AU - Alomar, Suliman Yousef

AU - Bonavita, Eduardo

AU - Galdiero, Maria Rosaria

AU - Garlanda, Cecilia

AU - Mantovani, Alberto

AU - Jaillon, Sebastien

PY - 2019/7/11

Y1 - 2019/7/11

N2 - 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. 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.

AB - 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. 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.

KW - carcinogenesis

KW - innate immunity

KW - interleukin-12

KW - macrophages

KW - neutrophils

KW - soft tissue sarcomas

KW - tumor immunology

KW - unconventional T cells

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U2 - 10.1016/j.cell.2019.05.047

DO - 10.1016/j.cell.2019.05.047

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