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    Neutrophils driving unconventional T cells mediate resistance against murine sarcomas and selected human tumors

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    Authors
    Ponzetta, A
    Carriero, 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
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    Affiliation
    Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele, Italy
    Issue Date
    2019
    
    Metadata
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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.
    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
    Cell
    URI
    http://hdl.handle.net/10541/621982
    DOI
    10.1016/j.cell.2019.05.047
    PubMed ID
    31257026
    Additional Links
    https://dx.doi.org/10.1016/j.cell.2019.05.047
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.cell.2019.05.047
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    All Paterson Institute for Cancer Research

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