@article{10.1172/jci.insight.125884, author = {Joanna Mikulak AND Ferdinando Oriolo AND Elena Bruni AND Alessandra Roberto AND Federico S. Colombo AND Anna Villa AND Marita Bosticardo AND Ileana Bortolomai AND Elena Lo Presti AND Serena Meraviglia AND Francesco Dieli AND Stefania Vetrano AND Silvio Danese AND Silvia Della Bella AND Michele M. Carvello 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 Biagio di Lorenzo AND Emanuela Marcenaro AND Bruno Silva-Santos AND Antonino Spinelli AND Domenico Mavilio}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {NKp46-expressing human gut-resident intraepithelial Vδ1 T cell subpopulation exhibits high antitumor activity against colorectal cancer}, year = {2019}, month = {12}, volume = {4}, url = {https://insight.jci.org/articles/view/125884}, 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.}, number = {24}, doi = {10.1172/jci.insight.125884}, url = {https://doi.org/10.1172/jci.insight.125884}, }