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NKp46-expressing human gut-resident intraepithelial Vδ1 T cell subpopulation exhibits high antitumor activity against colorectal cancer

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NKp46-expressing human gut-resident intraepithelial Vδ1 T cell subpopulation exhibits high antitumor activity against colorectal cancer. / Mikulak, Joanna; Oriolo, Ferdinando; Bruni, Elena; Roberto, Alessandra; Colombo, Federico S; Villa, Anna; Bosticardo, Marita; Bortolomai, Ileana; Lo Presti, Elena; Meraviglia, Serena; Dieli, Francesco; Vetrano, Stefania; Danese, Silvio; Della Bella, Silvia; Carvello, Michele M; Sacchi, Matteo; Cugini, Giovanni; Colombo, Giovanni; Klinger, Marco; Spaggiari, Paola; Roncalli, Massimo; Prinz, Immo; Ravens, Sarina; di Lorenzo, Biagio; Marcenaro, Emanuela; Silva-Santos, Bruno; Spinelli, Antonino; Mavilio, Domenico.

In: JCI INSIGHT, Vol. 4, No. 24, 19.12.2019.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Mikulak, J, Oriolo, F, Bruni, E, Roberto, A, Colombo, FS, Villa, A, Bosticardo, M, Bortolomai, I, Lo Presti, E, Meraviglia, S, Dieli, F, Vetrano, S, Danese, S, Della Bella, S, Carvello, MM, Sacchi, M, Cugini, G, Colombo, G, Klinger, M, Spaggiari, P, Roncalli, M, Prinz, I, Ravens, S, di Lorenzo, B, Marcenaro, E, Silva-Santos, B, Spinelli, A & Mavilio, D 2019, 'NKp46-expressing human gut-resident intraepithelial Vδ1 T cell subpopulation exhibits high antitumor activity against colorectal cancer', JCI INSIGHT, vol. 4, no. 24. https://doi.org/10.1172/jci.insight.125884

APA

Mikulak, J., Oriolo, F., Bruni, E., Roberto, A., Colombo, F. S., Villa, A., Bosticardo, M., Bortolomai, I., Lo Presti, E., Meraviglia, S., Dieli, F., Vetrano, S., Danese, S., Della Bella, S., Carvello, M. M., Sacchi, M., Cugini, G., Colombo, G., Klinger, M., ... Mavilio, D. (2019). NKp46-expressing human gut-resident intraepithelial Vδ1 T cell subpopulation exhibits high antitumor activity against colorectal cancer. JCI INSIGHT, 4(24). https://doi.org/10.1172/jci.insight.125884

Vancouver

Mikulak J, Oriolo F, Bruni E, Roberto A, Colombo FS, Villa A et al. NKp46-expressing human gut-resident intraepithelial Vδ1 T cell subpopulation exhibits high antitumor activity against colorectal cancer. JCI INSIGHT. 2019 Dec 19;4(24). https://doi.org/10.1172/jci.insight.125884

Bibtex

@article{91efced0063f40c28fdf309e6061c9d7,
title = "NKp46-expressing human gut-resident intraepithelial Vδ1 T cell subpopulation exhibits high antitumor activity against colorectal cancer",
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.",
keywords = "Adult, Age Factors, Aged, Aged, 80 and over, Animals, Antigens, Ly/metabolism, Colon/cytology, Colorectal Neoplasms/immunology, Disease Progression, Female, Humans, Ileum/cytology, Immunotherapy, Adoptive/methods, Intestinal Mucosa/cytology, Intraepithelial Lymphocytes/immunology, Male, Mice, Middle Aged, Natural Cytotoxicity Triggering Receptor 1/metabolism, Neoplasm Staging, Receptors, Antigen, T-Cell, gamma-delta/metabolism, Sex Hormone-Binding Globulin, T-Lymphocytes, Cytotoxic/immunology, Young Adult",
author = "Joanna Mikulak and Ferdinando Oriolo and Elena Bruni and Alessandra Roberto and Colombo, {Federico S} and Anna Villa and Marita Bosticardo and Ileana Bortolomai and {Lo Presti}, Elena and Serena Meraviglia and Francesco Dieli and Stefania Vetrano and Silvio Danese and {Della Bella}, Silvia and Carvello, {Michele M} and Matteo Sacchi and Giovanni Cugini and Giovanni Colombo and Marco Klinger and Paola Spaggiari and Massimo Roncalli and Immo Prinz and Sarina Ravens and {di Lorenzo}, Biagio and Emanuela Marcenaro and Bruno Silva-Santos and Antonino Spinelli and Domenico Mavilio",
year = "2019",
month = dec,
day = "19",
doi = "10.1172/jci.insight.125884",
language = "English",
volume = "4",
journal = "JCI INSIGHT",
issn = "2379-3708",
publisher = "The American Society for Clinical Investigation",
number = "24",

}

RIS

TY - JOUR

T1 - NKp46-expressing human gut-resident intraepithelial Vδ1 T cell subpopulation exhibits high antitumor activity against colorectal cancer

AU - Mikulak, Joanna

AU - Oriolo, Ferdinando

AU - Bruni, Elena

AU - Roberto, Alessandra

AU - Colombo, Federico S

AU - Villa, Anna

AU - Bosticardo, Marita

AU - Bortolomai, Ileana

AU - Lo Presti, Elena

AU - Meraviglia, Serena

AU - Dieli, Francesco

AU - Vetrano, Stefania

AU - Danese, Silvio

AU - Della Bella, Silvia

AU - Carvello, Michele M

AU - Sacchi, Matteo

AU - Cugini, Giovanni

AU - Colombo, Giovanni

AU - Klinger, Marco

AU - Spaggiari, Paola

AU - Roncalli, Massimo

AU - Prinz, Immo

AU - Ravens, Sarina

AU - di Lorenzo, Biagio

AU - Marcenaro, Emanuela

AU - Silva-Santos, Bruno

AU - Spinelli, Antonino

AU - Mavilio, Domenico

PY - 2019/12/19

Y1 - 2019/12/19

N2 - 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.

AB - 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.

KW - Adult

KW - Age Factors

KW - Aged

KW - Aged, 80 and over

KW - Animals

KW - Antigens, Ly/metabolism

KW - Colon/cytology

KW - Colorectal Neoplasms/immunology

KW - Disease Progression

KW - Female

KW - Humans

KW - Ileum/cytology

KW - Immunotherapy, Adoptive/methods

KW - Intestinal Mucosa/cytology

KW - Intraepithelial Lymphocytes/immunology

KW - Male

KW - Mice

KW - Middle Aged

KW - Natural Cytotoxicity Triggering Receptor 1/metabolism

KW - Neoplasm Staging

KW - Receptors, Antigen, T-Cell, gamma-delta/metabolism

KW - Sex Hormone-Binding Globulin

KW - T-Lymphocytes, Cytotoxic/immunology

KW - Young Adult

U2 - 10.1172/jci.insight.125884

DO - 10.1172/jci.insight.125884

M3 - SCORING: Journal article

C2 - 31689241

VL - 4

JO - JCI INSIGHT

JF - JCI INSIGHT

SN - 2379-3708

IS - 24

ER -