iNKT cells account for a relevant fraction of effector T-cells in the intestine and are considered an attractive platform for cancer immunotherapy. Although iNKT cells are cytotoxic lymphocytes, their functional role in colorectal cancer (CRC) is still controversial, limiting their therapeutic use. Thus, we examined the immune cell composition and iNKT cell phenotype of CRC lesions in patients (n = 118) and different murine models. High-dimensional single-cell flow-cytometry, metagenomics, and RNA sequencing experiments revealed that iNKT cells are enriched in tumor lesions. The tumor-associated pathobiont Fusobacterium nucleatum induces IL-17 and Granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in iNKT cells without affecting their cytotoxic capability but promoting iNKT-mediated recruitment of neutrophils with polymorphonuclear myeloid-derived suppressor cells-like phenotype and functions. The lack of iNKT cells reduced the tumor burden and recruitment of immune suppressive neutrophils. iNKT cells in-vivo activation with α-galactosylceramide restored their anti-tumor function, suggesting that iNKT cells can be modulated to overcome CRC-associated immune evasion. Tumor co-infiltration by iNKT cells and neutrophils correlates with negative clinical outcomes, highlighting the importance of iNKT cells in the pathophysiology of CRC. Our results reveal a functional plasticity of iNKT cells in CRC, suggesting a pivotal role of iNKT cells in shaping the tumor microenvironment, with relevant implications for treatment.

Lattanzi, G., Strati, F., Díaz-Basabe, A., Perillo, F., Amoroso, C., Protti, G., et al. (2023). iNKT cell-neutrophil crosstalk promotes colorectal cancer pathogenesis. MUCOSAL IMMUNOLOGY, 16(3 (June 2023)), 326-340 [10.1016/j.mucimm.2023.03.006].

iNKT cell-neutrophil crosstalk promotes colorectal cancer pathogenesis

Strati, Francesco;Protti, Giulia;Baeri, Alberto;Granucci, Francesca;Facciotti, Federica
2023

Abstract

iNKT cells account for a relevant fraction of effector T-cells in the intestine and are considered an attractive platform for cancer immunotherapy. Although iNKT cells are cytotoxic lymphocytes, their functional role in colorectal cancer (CRC) is still controversial, limiting their therapeutic use. Thus, we examined the immune cell composition and iNKT cell phenotype of CRC lesions in patients (n = 118) and different murine models. High-dimensional single-cell flow-cytometry, metagenomics, and RNA sequencing experiments revealed that iNKT cells are enriched in tumor lesions. The tumor-associated pathobiont Fusobacterium nucleatum induces IL-17 and Granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in iNKT cells without affecting their cytotoxic capability but promoting iNKT-mediated recruitment of neutrophils with polymorphonuclear myeloid-derived suppressor cells-like phenotype and functions. The lack of iNKT cells reduced the tumor burden and recruitment of immune suppressive neutrophils. iNKT cells in-vivo activation with α-galactosylceramide restored their anti-tumor function, suggesting that iNKT cells can be modulated to overcome CRC-associated immune evasion. Tumor co-infiltration by iNKT cells and neutrophils correlates with negative clinical outcomes, highlighting the importance of iNKT cells in the pathophysiology of CRC. Our results reveal a functional plasticity of iNKT cells in CRC, suggesting a pivotal role of iNKT cells in shaping the tumor microenvironment, with relevant implications for treatment.
Articolo in rivista - Articolo scientifico
CRC; Fusobacterium nucleatum; iNKT cells; neutrophils
English
31-mar-2023
2023
16
3 (June 2023)
326
340
open
Lattanzi, G., Strati, F., Díaz-Basabe, A., Perillo, F., Amoroso, C., Protti, G., et al. (2023). iNKT cell-neutrophil crosstalk promotes colorectal cancer pathogenesis. MUCOSAL IMMUNOLOGY, 16(3 (June 2023)), 326-340 [10.1016/j.mucimm.2023.03.006].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/409481
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