{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:27:44Z","timestamp":1777354064669,"version":"3.51.4"},"reference-count":50,"publisher":"American Society of Hematology","issue":"4","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,7,28]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The success of cancer immunotherapy depends on productive tumor cell recognition by killer lymphocytes. \u03b3\u03b4 T cells are a population of innate-like lymphocytes endowed with strong, MHC-unrestricted cytotoxicity against tumor cells. This notwithstanding, we recently showed that a large proportion of human hematologic tumors is resistant to \u03b3\u03b4 peripheral blood lymphocytes (PBLs) activated with specific agonists to the highly prevalent V\u03b39V\u03b42 TCR. Although this probably constitutes an important limitation to current \u03b3\u03b4 T cell\u2013mediated immunotherapy strategies, we describe here the differentiation of a novel subset of V\u03b42\u2212 V\u03b41+ PBLs expressing natural cytotoxicity receptors (NCRs) that directly mediate killing of leukemia cell lines and chronic lymphocytic leukemia patient neoplastic cells. We show that V\u03b41+ T cells can be selectively induced to express NKp30, NKp44 and NKp46, through a process that requires functional phosphatidylinositol 3-kinase (PI-3K)\/AKT signaling on stimulation with \u03b3c cytokines and TCR agonists. The stable expression of NCRs is associated with high levels of granzyme B and enhanced cytotoxicity against lymphoid leukemia cells. Specific gain-of-function and loss-of-function experiments demonstrated that NKp30 makes the most important contribution to TCR-independent leukemia cell recognition. Thus, NKp30+ V\u03b41+ T cells constitute a novel, inducible and specialized killer lymphocyte population with high potential for immunotherapy of human cancer.<\/jats:p>","DOI":"10.1182\/blood-2011-02-339135","type":"journal-article","created":{"date-parts":[[2011,6,3]],"date-time":"2011-06-03T04:45:24Z","timestamp":1307076324000},"page":"992-1001","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":203,"title":["Differentiation of human peripheral blood V\u03b41+ T cells expressing the natural cytotoxicity receptor NKp30 for recognition of lymphoid leukemia cells"],"prefix":"10.1182","volume":"118","author":[{"given":"Daniel V.","family":"Correia","sequence":"first","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal;"},{"name":"Instituto Gulbenkian de Ci\u00eancia, Oeiras, Portugal;"}]},{"given":"Manuela","family":"Fogli","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Immunology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Clinico Humanitas, Milan, Italy; and"}]},{"given":"Kelly","family":"Hudspeth","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Immunology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Clinico Humanitas, Milan, Italy; and"}]},{"given":"Maria Gomes","family":"da Silva","sequence":"additional","affiliation":[{"name":"Instituto Portugu\u00eas de Oncologia de Lisboa, Francisco Gentil, Lisbon, Portugal"}]},{"given":"Domenico","family":"Mavilio","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Experimental Immunology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Clinico Humanitas, Milan, Italy; and"}]},{"given":"Bruno","family":"Silva-Santos","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal;"},{"name":"Instituto Gulbenkian de Ci\u00eancia, Oeiras, Portugal;"}]}],"member":"234","reference":[{"key":"2019111807450969000_B1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1146\/annurev-immunol-031210-101324","article-title":"Natural innate and adaptive immunity to cancer.","volume":"29","author":"Vesely","year":"2011","journal-title":"Annu Rev Immunol"},{"issue":"12","key":"2019111807450969000_B2","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1182\/blood-2009-08-237123","article-title":"The MHC class Ib protein ULBP1 is a nonredundant determinant of leukemia\/lymphoma susceptibility to gammadelta T-cell 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