Natural killer (NK) cells express surface receptors that regulate potent effector functions, such as cytolytic activity and release of cytokines, which play a central role in inflammatory response and immunoregulation. In this paper, major advances are outlined from the original discovery of HLA-class I-specific inhibitory receptors in humans to recent, particularly successful, clinical applications in the cure of high-risk, otherwise fatal leukaemias. The central role of donor-derived “alloreactive” NK cells in eradicating leukaemic cells in the T-cell-depleted haploidentical haematopoietic stem cell transplantation setting became evident. Since alloreactive NK cells seem to play a key role also in preventing graft rejection and graft-vs-host disease, they may be an ideal tool to treat high-risk leukaemias in the haematopoietic stem cell transplantation setting.
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Funding: This work was supported by grants awarded by Associazione Italiana per la Ricerca sul Cancro (AIRC), the Istituto Superiore di Sanità (ISS), Ministero della Salute (Ricerca Finalizzata Ministeriale 2005 “Caratterizzazione delle proprietà di immunomodulazione delle cellule staminali mesenchimali e possible applicazione nel trattamento delle malattie autoimmuni”), Ministero dell’Università e della Ricerca Scientifica e Tecnologica (MIUR - PRIN 2005, project 2005063024_004), FIRB-MIUR project-RBNE017B4 and European Union FP6, LSHB-CT-2004-503319-AlloStem (the European Commission is not liable for any use that may be made of the information contained). Also the financial support of Fondazione Compagnia di San Paolo, Torino, Italy, of Fondazione CARIGE and Fondazione CARIPLO is gratefully acknowledged.
Competing interests: None.