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BRIEF REVIEWS |
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* Institute of Histology and Laboratory Analysis,
Flow Cytometry and Cytomorphology Center,
Institute of Morphological Sciences, University of Urbino, Urbino, Italy;
Instituto Nazionale di Fisica Nucleare Gran Sasso National Laboratory, L’Aquila, Italy;
¶ Department of Normal Human Morphology, University of Trieste, Trieste, Italy;
|| Department of Anatomy, Pharmacology, and Forensic Medicine, University Hospital, University of Parma, Parma, Italy; and
# Department of Anatomical Sciences, University of Bologna, Bologna, Italy
In this review, we overview the main features and functions of NK cells, focusing on their role in cell-mediated immune response to tumor cells. In parallel, we discuss the information available in the field of NK cell receptors and offer a wide general overview of functional aspects of cell targeting and killing, focusing on the recent acknowledgments on the efficacy of NK cells after cytokine and mAb administration in cancer therapy. Since efficacy of NK cell-based immunotherapy has been proven in KIR-mismatch regimens or in TRAIL-dependent apoptosis, the ability to manipulate the balance of activating and inhibitory receptors on NK cells and of their cognate ligands, as well as the sensitivity of tumor cells to apoptosis, opens new perspectives for NK cell-based immunotherapy.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work is supported by Fondo per gli Investimenti della Ricerca di Base and Cofin Ministero dell’ Universitá e della Ricerca, Cassa di Risparmio di Bologna Foundation, and Cryopreserved cells and Ionizing Radiation, Instituto Nazionale di Fisica Nucleare project. Research described in this article was also supported in part by Philip Morris USA and Philip Morris International.
2 Address correspondence and reprint requests to Dr. Marco Vitale, Department of Anatomy, Pharmacology, and Forensic Medicine, University Hospital, Via Gramsci, 14, I-43100 Parma, Italy; E-mail address: marco.vitale@unipr.it or Dr. Loris Zamai, Institute of Histology and Laboratory Analysis, University of Urbino, Via Ubaldini 7, I-61020 Urbino, Italy; E-mail address: l.zamai{at}uniurb.it
3 Abbreviations used in this paper: MHC-I, MHC class I; AICD, activation-induced cell death; ADCC, Ab-dependent cellular cytotoxicity; DC, dendritic cell; FasL, Fas ligand; Flt3-L, Flt3-ligand; KIR, killer Ig-like receptor; LAK, lymphokine-activated killer; MEL, melanoma; RCC, renal cell carcinoma; SCF, stem cell factor; DNAM-1, DNAX accessory molecule 1.
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