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NKp46-expressing human gut-resident intraepithelial Vδ1 T cell subpopulation exhibits high antitumor activity against colorectal cancer.
- Source :
-
JCI insight [JCI Insight] 2019 Dec 19; Vol. 4 (24). Date of Electronic Publication: 2019 Dec 19. - Publication Year :
- 2019
-
Abstract
- γδ T cells account for a large fraction of human intestinal intraepithelial lymphocytes (IELs) endowed with potent antitumor 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, and intestine, either disease-free, affected by CRC, or generated from thymic precursors. The constitutive expression of NKp46 specifically identifies a subset of cytotoxic Vδ1 T cells representing the largest fraction of gut-resident IELs. The ontogeny and gut-tropism of NKp46+/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 antitumor functions. Higher frequencies of NKp46+/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 NKp46+/Vδ1 cells from activated thymic precursors. These results parallel the very low frequencies of NKp46+/Vδ1 IELs able to infiltrate CRC, thus providing insights to either follow-up cancer progression or to develop adoptive cellular therapies.
- Subjects :
- Adult
Age Factors
Aged
Aged, 80 and over
Animals
Antigens, Ly metabolism
Colon cytology
Colon immunology
Colorectal Neoplasms pathology
Colorectal Neoplasms therapy
Disease Progression
Female
Humans
Ileum cytology
Ileum immunology
Immunotherapy, Adoptive methods
Intestinal Mucosa immunology
Intraepithelial Lymphocytes metabolism
Intraepithelial Lymphocytes transplantation
Male
Mice
Middle Aged
Neoplasm Staging
Receptors, Antigen, T-Cell, gamma-delta metabolism
Sex Hormone-Binding Globulin
T-Lymphocytes, Cytotoxic metabolism
T-Lymphocytes, Cytotoxic transplantation
Young Adult
Colorectal Neoplasms immunology
Intestinal Mucosa cytology
Intraepithelial Lymphocytes immunology
Natural Cytotoxicity Triggering Receptor 1 metabolism
T-Lymphocytes, Cytotoxic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2379-3708
- Volume :
- 4
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- JCI insight
- Publication Type :
- Academic Journal
- Accession number :
- 31689241
- Full Text :
- https://doi.org/10.1172/jci.insight.125884