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

Andrea Ponzetta, Roberta Carriero, Silvia Carnevale, Marialuisa Barbagallo, Martina Molgora, Chiara Perucchini, Elena Magrini, Francesca Gianni, Paolo Kunderfranco, Nadia Polentarutti, Fabio Pasqualini, Sabrina Di Marco, Domenico Supino, Clelia Peano, Ferdinando Cananzi, Piergiuseppe Colombo, Silvana Pilotti, Suliman Yousef Alomar, Eduardo Bonavita, Maria Rosaria GaldieroCecilia Garlanda, Alberto Mantovani, Sebastien Jaillon

Research output: Contribution to journalArticlepeer-review

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.

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

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