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

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

Cell (2019-07-02)
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 Galdiero, Cecilia Garlanda, Alberto Mantovani, Sebastien Jaillon
PMID31257026
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.