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

Elena Lo Presti, Francesco Dieli, Serena Meraviglia, Ileana Bortolomai, Michele M. Carvello, Sarina Ravens, Anna Villa, Matteo Sacchi, Alessandra Roberto, Paola Spaggiari, Biagio Di Lorenzo, Giovanni Cugini, Giovanni Colombo, Ferdinando Oriolo, Elena Bruni, Silvio Danese, Marco Klinger, Silvia Della Bella, Michele M. Carvello, Silvia Della BellaBruno Silva-Santos, Marita Bosticardo, Joanna Mikulak, Immo Prinz, Stefania Vetrano, Domenico Mavilio, Emanuela Marcenaro, Silvio Danese, Massimo Roncalli, Federico S. Colombo, Antonino Spinelli, Marco Klinger

Risultato della ricerca: Articlepeer review

43 Citazioni (Scopus)


γδ 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.
Lingua originaleEnglish
pagine (da-a)1-42
Numero di pagine42
RivistaJCI insight
Stato di pubblicazionePublished - 2019

All Science Journal Classification (ASJC) codes

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