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.

Human intestinal and circulating invariant Natural Killer T cells are cytotoxic against colorectal cancer cells via the perforin-granzyme pathway / A. Díaz-Basabe, C. Burrello, G. Lattanzi, F. Botti, A. Carrara, E. Cassinotti, F. Caprioli, F. Facciotti. - In: MOLECULAR ONCOLOGY. - ISSN 1574-7891. - (2021). [Epub ahead of print] [10.1002/1878-0261.13104]

Human intestinal and circulating invariant Natural Killer T cells are cytotoxic against colorectal cancer cells via the perforin-granzyme pathway

A. Díaz-Basabe;C. Burrello;G. Lattanzi;F. Botti;A. Carrara;F. Caprioli;
2021

Abstract

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.
CD1d; colorectal cancer; cytotoxicity; iNKT; perforin
Settore MED/12 - Gastroenterologia
Settore MED/04 - Patologia Generale
Settore MED/18 - Chirurgia Generale
Settore MED/06 - Oncologia Medica
18-set-2021
Article (author)
File in questo prodotto:
File Dimensione Formato  
1878-0261.13104.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 3.11 MB
Formato Adobe PDF
3.11 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/871622
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 2
social impact