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NK cells express HLA class I-specific inhibitory receptors and preferentially kill HLA class Ilow tumors or virus-infected cells. Killing occurs upon engagement of activating NKRs with ligands that are up-regulated on tumors and infected cells. A similar activating receptor\/ligand interaction strategy is used by \u03b3\u03b4 T cells, which in addition, use their TCRs for recognition of phosphorylated antigens and still largely undefined ligands on tumor cells. In the haploidentical allo-HSCT setting, alloreactive NK cells, derived from donor HSCs, can exert potent antileukemia activity and kill residual patient DCs and T cells, thus preventing GvHD and graft rejection. However, generation of KIR+ alloreactive NK cells from HSCs requires many weeks, during which leukemia relapses, and life-threatening infections may occur. Importantly, mature NK cells and \u03b3\u03b4 T cells can control certain infectious agents efficiently, in particular, limit CMV reactivation, and infusion of such donor cells at the time of HSCT has been implemented. Development of novel, cell-based immunotherapies, allowing improved trafficking and better targeting, will endow NK cells and \u03b3\u03b4 T lymphocytes with enhanced anti-tumor activity, also making them key reagents for therapies against solid tumors. The clinical aspects of using NK cells and \u03b3\u03b4 T lymphocytes against hematological malignancies, including the allo-HSCT context, are reviewed in the related side-by-side paper by Locatelli and colleagues [1].<\/jats:p>","DOI":"10.1189\/jlb.0613312","type":"journal-article","created":{"date-parts":[[2013,10,10]],"date-time":"2013-10-10T14:25:35Z","timestamp":1381415135000},"page":"1123-1139","source":"Crossref","is-referenced-by-count":36,"title":["At the Bench: Preclinical rationale for exploiting NK cells and \u03b3\u03b4 T lymphocytes for the treatment of high-risk leukemias"],"prefix":"10.1093","volume":"94","author":[{"given":"H\u00e5kan","family":"Norell","sequence":"first","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , Lisbon, Portugal"}]},{"given":"Alessandro","family":"Moretta","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale and Centro di Eccellenza per le Ricerche Biomediche, Universita degli Studi di Genova , Italy"}]},{"given":"Bruno","family":"Silva-Santos","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , Lisbon, Portugal"}]},{"given":"Lorenzo","family":"Moretta","sequence":"additional","affiliation":[{"name":"Istituto Giannina Gaslini , Genoa, Italy"}]}],"member":"286","published-online":{"date-parts":[[2013,10,9]]},"reference":[{"key":"2023032711173221500_","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1189\/jlb.0613343","article-title":"At the bedside: innate immunity as an immunotherapy tool for hematological malignancies","volume":"94","author":"Locatelli","year":"2013","journal-title":"J. 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