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Englishγδ T cells account for a large fraction of human intestinal intraepithelial lymphocytes (IELs) endowed with potent anti-tumor activities. However, little is known about their origin, phenotype and clinical relevance in colorectal cancer (CRC). To determine γδ IEL gut-specificity, homing and functions, γδ T cells were purified from human healthy blood, lymph nodes, liver, skin, intestine either disease-free or affected by CRC or generated from thymic precursors. The constitutive expression of NKp46 specifically identifies a new subset of cytotoxic Vδ1 T cells representing the largest fraction of gut-resident IELs. The ontogeny and gut-tropism of NKp46pos/Vδ1 IELs depends both on distinctive features of Vδ1 thymic precursors and gut-environmental factors. Either the constitutive presence of NKp46 on tissue-resident Vδ1 intestinal IELs or its induced-expression on IL-2/IL-15 activated Vδ1 thymocytes are associated with anti-tumor functions. Higher frequencies of NKp46pos/Vδ1 IELs in tumor-free specimens from CRC patients correlate with a lower risk of developing metastatic III/IV disease stages. Additionally, our in vitro settings reproducing CRC tumor-microenvironment inhibited the expansion of NKp46pos/Vδ1 cells from activated thymic precursors. These results parallel the very low frequencies of NKp46pos/Vδ1 IELs able to infiltrate CRC, thus providing new insights to either follow-up cancer progression or develop novel adoptive cellular therapies.
NKp46-expressing human gut-resident intraepithelial Vδ1 T cell subpopulation exhibits high anti-tumor activity against colorectal cancer / J. Mikulak, F. Oriolo, E. Bruni, A. Roberto, F.S. Colombo, A. Villa, M. Bosticardo, I. Bortolomai, E. Lo Presti, S. Meraviglia, F. Dieli, S. Vetrano, S. Danese, S. Della Bella, M.M. Carvello, M. Sacchi, G. Cugini, G. Colombo, M. Klinger, P. Spaggiari, M. Roncalli, I. Prinz, S. Ravens, B. di Lorenzo, E. Marcenaro, B. Silva-Santos, A. Spinelli, D. Mavilio. - In: JCI INSIGHT. - ISSN 2379-3708. - 4:24(2019 Dec).
| Titolo: | NKp46-expressing human gut-resident intraepithelial Vδ1 T cell subpopulation exhibits high anti-tumor activity against colorectal cancer |
| Autori: | MIKULAK, JOANNA (Primo) ORIOLO, FERDINANDO (Secondo) SPINELLI, ANTONINO (Penultimo) MAVILIO, DOMENICO (Ultimo) |
| Parole Chiave: | Colorectal cancer; Gastroenterology; Immunology; Innate immunity; T cells |
| Settore Scientifico Disciplinare: | Settore MED/46 - Scienze Tecniche di Medicina di Laboratorio Settore MED/04 - Patologia Generale Settore MED/12 - Gastroenterologia Settore MED/06 - Oncologia Medica |
| Data di pubblicazione: | dic-2019 |
| Rivista: | |
| Tipologia: | Article (author) |
| Data ahead of print / Data di stampa: | 5-nov-2019 |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1172/jci.insight.125884 |
| Appare nelle tipologie: | 01 - Articolo su periodico |
File in questo prodotto:
| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| L:Mikulak et al. - JCI Insights (on line version).pdf | Post-print, accepted manuscript ecc. (versione accettata dall'editore) | Open Access Visualizza/Apri | ||
| 125884.2-20191216101749-covered-253bed37ca4c1ab43d105aefdf7b5536.pdf | Publisher's version/PDF | Open Access Visualizza/Apri |
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