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Neutrophils driving unconventional T cells mediate resistance against murine sarcomas and selected human tumors
Ponzetta, A Carriero, R Carnevale, S Barbagallo, M Molgora, M Perucchini, C Magrini, E Gianni, F Kunderfranco, P Polentarutti, N
Ponzetta, A
Carriero, R
Carnevale, S
Barbagallo, M
Molgora, M
Perucchini, C
Magrini, E
Gianni, F
Kunderfranco, P
Polentarutti, N
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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-gamma-dependent pathway of immune resistance, associated with polarization of a subset of CD4(-) CD8(-) unconventional alphabeta T cells (UTCalphabeta). Bulk and single-cell RNA sequencing (scRNA-seq) analyses unveiled the innate-like features and diversity of UTCalphabeta 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 UTCalphabeta polarization and type 1 immunity are essential for resistance against murine sarcomas and selected human tumors.
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Date
2019
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Citation
Ponzetta A, Carriero R, Carnevale S, Barbagallo M, Molgora M, Perucchini C, et al. Neutrophils driving unconventional T cells mediate resistance against murine sarcomas and selected human tumors. Cell. 2019 Jul 11;178(2):346-60 e24.