Neutrophils driving unconventional T cells mediate resistance against murine sarcomas and selected human tumors
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Authors
Ponzetta, ACarriero, R
Carnevale, S
Barbagallo, M
Molgora, M
Perucchini, C
Magrini, E
Gianni, F
Kunderfranco, P
Polentarutti, N
Pasqualini, F
Di Marco, S
Supino, D
Peano, C
Cananzi, F
Colombo, P
Pilotti, S
Alomar, SY
Bonavita, Eduardo
Galdiero, MR
Garlanda, C
Mantovani, A
Jaillon, S
Affiliation
Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele, ItalyIssue Date
2019
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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.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.Journal
CellDOI
10.1016/j.cell.2019.05.047PubMed ID
31257026Additional Links
https://dx.doi.org/10.1016/j.cell.2019.05.047Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1016/j.cell.2019.05.047
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