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.; Pasqualini, F.; Di Marco, S.; Supino, D.; Peano, C.; Cananzi, F.; Colombo, P.; Pilotti, S.; Alomar, S. Y.; Bonavita, E.; Galdiero, M. R.; Garlanda, C.; Mantovani, A.; Jaillon, S.

doi:10.1016/j.cell.2019.05.047

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.

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., Pasqualini, F., Di Marco, S., Supino, D., Peano, C., Cananzi, F., Colombo, P., Pilotti, S., Alomar, S.Y., Bonavita, E., Galdiero, M.R., et al.. - In: CELL. - ISSN 0092-8674. - 178:2(2019), pp. 346-360.e24. [10.1016/j.cell.2019.05.047]