Human intestinal and circulating invariant natural killer T cells are cytotoxic against colorectal cancer cells via the perforin–granzyme pathway

Invariant natural killer T (iNKT) cells are lipid‐specific T lymphocytes endowed with cytotoxic activities and are thus considered important in antitumor immunity. While several studies have demonstrated iNKT cell cytotoxicity against different tumors, very little is known about their cell‐killing a...

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Autores principales:	Angélica Díaz‐Basabe, Claudia Burrello, Georgia Lattanzi, Fiorenzo Botti, Alberto Carrara, Elisa Cassinotti, Flavio Caprioli, Federica Facciotti
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	CD1d colorectal cancer cytotoxicity iNKT perforin Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/c8cd6bf6609248f79a02e8de99757ec0
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spelling	oai:doaj.org-article:c8cd6bf6609248f79a02e8de99757ec02021-12-02T10:31:06ZHuman intestinal and circulating invariant natural killer T cells are cytotoxic against colorectal cancer cells via the perforin–granzyme pathway1878-02611574-789110.1002/1878-0261.13104https://doaj.org/article/c8cd6bf6609248f79a02e8de99757ec02021-12-01T00:00:00Zhttps://doi.org/10.1002/1878-0261.13104https://doaj.org/toc/1574-7891https://doaj.org/toc/1878-0261Invariant natural killer T (iNKT) cells are lipid‐specific T lymphocytes endowed with cytotoxic activities and are thus considered important in antitumor immunity. While several studies have demonstrated iNKT cell cytotoxicity against different tumors, very little is known about their cell‐killing activities in human colorectal cancer (CRC). Our aim was to assess whether human iNKT cells are cytotoxic against colon cancer cells and the mechanisms underlying this activity. For this purpose, we generated stable iNKT cell lines from peripheral blood and colon specimens and used NK‐92 and peripheral blood natural killer cells as cell‐mediated cytotoxicity controls. In vitro cytotoxicity was assessed using a panel of well‐characterized human CRC cell lines, and the cellular requirements for iNKT cell cytotoxic functions were evaluated. We demonstrated that both intestinal and circulating iNKT cells were cytotoxic against the entire panel of CRC lines, as well as against freshly isolated patient‐derived colonic epithelial cancer cells. Perforin and/or granzyme inhibition impaired iNKT cell cytotoxicity, whereas T‐cell receptor (TCR) signaling was a less stringent requirement for efficient killing. This study is the first evidence of tissue‐derived iNKT cell cytotoxic activity in humans, as it shows that iNKT cells depend on the perforin–granzyme pathway and both adaptive and innate signal recognition for proper elimination of colon cancer cells.Angélica Díaz‐BasabeClaudia BurrelloGeorgia LattanziFiorenzo BottiAlberto CarraraElisa CassinottiFlavio CaprioliFederica FacciottiWileyarticleCD1dcolorectal cancercytotoxicityiNKTperforinNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Oncology, Vol 15, Iss 12, Pp 3385-3403 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CD1d colorectal cancer cytotoxicity iNKT perforin Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	CD1d colorectal cancer cytotoxicity iNKT perforin Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Angélica Díaz‐Basabe Claudia Burrello Georgia Lattanzi Fiorenzo Botti Alberto Carrara Elisa Cassinotti Flavio Caprioli Federica Facciotti Human intestinal and circulating invariant natural killer T cells are cytotoxic against colorectal cancer cells via the perforin–granzyme pathway
description	Invariant natural killer T (iNKT) cells are lipid‐specific T lymphocytes endowed with cytotoxic activities and are thus considered important in antitumor immunity. While several studies have demonstrated iNKT cell cytotoxicity against different tumors, very little is known about their cell‐killing activities in human colorectal cancer (CRC). Our aim was to assess whether human iNKT cells are cytotoxic against colon cancer cells and the mechanisms underlying this activity. For this purpose, we generated stable iNKT cell lines from peripheral blood and colon specimens and used NK‐92 and peripheral blood natural killer cells as cell‐mediated cytotoxicity controls. In vitro cytotoxicity was assessed using a panel of well‐characterized human CRC cell lines, and the cellular requirements for iNKT cell cytotoxic functions were evaluated. We demonstrated that both intestinal and circulating iNKT cells were cytotoxic against the entire panel of CRC lines, as well as against freshly isolated patient‐derived colonic epithelial cancer cells. Perforin and/or granzyme inhibition impaired iNKT cell cytotoxicity, whereas T‐cell receptor (TCR) signaling was a less stringent requirement for efficient killing. This study is the first evidence of tissue‐derived iNKT cell cytotoxic activity in humans, as it shows that iNKT cells depend on the perforin–granzyme pathway and both adaptive and innate signal recognition for proper elimination of colon cancer cells.
format	article
author	Angélica Díaz‐Basabe Claudia Burrello Georgia Lattanzi Fiorenzo Botti Alberto Carrara Elisa Cassinotti Flavio Caprioli Federica Facciotti
author_facet	Angélica Díaz‐Basabe Claudia Burrello Georgia Lattanzi Fiorenzo Botti Alberto Carrara Elisa Cassinotti Flavio Caprioli Federica Facciotti
author_sort	Angélica Díaz‐Basabe
title	Human intestinal and circulating invariant natural killer T cells are cytotoxic against colorectal cancer cells via the perforin–granzyme pathway
title_short	Human intestinal and circulating invariant natural killer T cells are cytotoxic against colorectal cancer cells via the perforin–granzyme pathway
title_full	Human intestinal and circulating invariant natural killer T cells are cytotoxic against colorectal cancer cells via the perforin–granzyme pathway
title_fullStr	Human intestinal and circulating invariant natural killer T cells are cytotoxic against colorectal cancer cells via the perforin–granzyme pathway
title_full_unstemmed	Human intestinal and circulating invariant natural killer T cells are cytotoxic against colorectal cancer cells via the perforin–granzyme pathway
title_sort	human intestinal and circulating invariant natural killer t cells are cytotoxic against colorectal cancer cells via the perforin–granzyme pathway
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/c8cd6bf6609248f79a02e8de99757ec0
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Human intestinal and circulating invariant natural killer T cells are cytotoxic against colorectal cancer cells via the perforin–granzyme pathway

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