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

A Ponzetta, R Carriero, S Carnevale, M Barbagallo… - Cell, 2019 - cell.com
A Ponzetta, R Carriero, S Carnevale, M Barbagallo, M Molgora, C Perucchini, E Magrini…
Cell, 2019cell.com
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 (UTC αβ). Bulk and single-cell RNA …
Summary
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.
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