期刊
CELL
卷 178, 期 2, 页码 346-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2019.05.047
关键词
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资金
- European Research Council (ERC project) [PHII-669415]
- Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR) [PRIN 2015YYKPNN]
- Deanship of Scientific Research at King Saud University [PEJP-18-11]
- Fondazione AIRC per la Ricerca sul Cancro [AIRC IG-19014, AIRC 5x1000-9962, AIRC ID18475]
- Fondazione Italiana per la Ricerca sul Cancro (FIRC)
- Fondazione Umberto Veronesi (FUV)
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 alpha beta T cells (UTC alpha beta). Bulk and single-cell RNA sequencing (scRNA-seq) analyses unveiled the innate-like features and diversity of UTC alpha beta 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 UTC alpha beta polarization and type 1 immunity are essential for resistance against murine sarcomas and selected human tumors.
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