NDLI: Cutting edge: tumor-targeting antibodies enhance NKG2D-mediated NK cell cytotoxicity by stabilizing NK cell-tumor cell interactions.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lemaître, Fabrice Bousso, Philippe Deguine, Jacques Breart, Béatrice
Description	Country affiliation: France Author Affiliation: Deguine J ( Dynamics of Immune Responses Unit, Institut Pasteur, 75015 Paris, France.)
Abstract	Monoclonal antibodies represent a promising approach to fight a variety of tumors, but their mode of action remains to be fully understood. NK cells can recognize Ab-coated targets, as well as stress ligands, on tumor cells. In this study, we investigated how NK cells integrate both kinds of activating signals. NK cell-mediated killing was maximal with the combined recognition of NKG2D ligands and Ab; surprisingly, only NKG2D engagement substantially enhanced degranulation. Conversely, Ab recognition by NK cells uniquely increased contact stability with tumor cells. Furthermore, using intravital imaging of solid tumors, we showed that Ab recognition favored prolonged interactions between NK cells and targets. Altogether, our results demonstrate that NK cell-mediated killing can be differentially regulated at the level of degranulation and contact stability by distinct activating receptors. Thus, complementary signals mediated by recognition of stress ligands and tumor-specific Abs may contribute to the efficacy of NK cells during mAb therapy.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	12
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-12-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antibodies, Neoplasm Pharmacology Antibody-dependent Cell Cytotoxicity Immunology Cell Communication Nk Cell Lectin-like Receptor Subfamily K Physiology Up-regulation Animals Cell Degranulation Cell Line, Tumor Coculture Techniques Gene Knock-in Techniques Killer Cells, Natural Metabolism Pathology Lymphoma Mice Mice, Inbred C57bl Mice, Knockout Receptors, Igg Thymoma Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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