HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Poggi, A. Articles by Zocchi, M. R. Search for Related Content PubMed PubMed Citation Articles by Poggi, A. Articles by Zocchi, M. R.

Tumor-Induced Apoptosis of Human IL-2-Activated NK Cells: Role of Natural Cytotoxicity Receptors¹

Alessandro Poggi^2,*, Anna-Maria Massaro^*,, Simone Negrini, Paola Contini and Maria Raffaella Zocchi

^* Laboratory of Immunology, National Institute for Cancer Research, and Laboratory of Clinical Immunology, Department of Internal Medicine, University of Genoa, Genoa, Italy; and Laboratory of Tumor Immunology, Scientific Institute San Raffaele, Milan, Italy

We provide evidence that tumor cells can induce apoptosis of NK cells by engaging the natural cytotoxicity receptors (NCR) NKp30, NKp44, and NKp46. Indeed, the binding between NCR on NK cells and their putative ligands on tumor target cells led to NK cell apoptosis, and this event was abolished by blocking NCR/NCR-ligand interaction by anti-NCR-specific mAbs. The engagement of NCR induced up-regulation of Fas ligand (FasL) mRNA, FasL protein synthesis, and release. In turn, FasL interacting with Fas at NK cell surface causes NK cell suicide, as apoptosis of NK cells was inhibited by blocking FasL/Fas interaction with specific mAbs. Interestingly, NK cell apoptosis, but not killing of tumor target cells, is inhibited by cyclosporin A, suggesting that apoptosis and cytolysis are regulated by different biochemical pathways. These findings indicate that NCR are not only triggering molecules essential for antitumor activity, but also surface receptors involved in NK cell suicide.

This article has been cited by other articles:

				Q. Tang, B. Grzywacz, H. Wang, N. Kataria, Q. Cao, J. E. Wagner, B. R. Blazar, J. S. Miller, and M. R. Verneris Umbilical Cord Blood T Cells Express Multiple Natural Cytotoxicity Receptors after IL-15 Stimulation, but Only NKp30 Is Functional J. Immunol., October 1, 2008; 181(7): 4507 - 4515. [Abstract] [Full Text] [PDF]

				H. Wang, B. Grzywacz, D. Sukovich, V. McCullar, Q. Cao, A. B. Lee, B. R. Blazar, D. N. Cornfield, J. S. Miller, and M. R. Verneris The unexpected effect of cyclosporin A on CD56+CD16 and CD56+CD16+ natural killer cell subpopulations Blood, September 1, 2007; 110(5): 1530 - 1539. [Abstract] [Full Text] [PDF]

				S. Wittnebel, S. Da Rocha, J. Giron-Michel, A. Jalil, P. Opolon, B. Escudier, P. Validire, K. Khawam, S. Chouaib, B. Azzarone, et al. Membrane-Bound Interleukin (IL)-15 on Renal Tumor Cells Rescues Natural Killer Cells from IL-2 Starvation-Induced Apoptosis Cancer Res., June 15, 2007; 67(12): 5594 - 5599. [Abstract] [Full Text] [PDF]

				A. Poggi, C. Prevosto, A.-M. Massaro, S. Negrini, S. Urbani, I. Pierri, R. Saccardi, M. Gobbi, and M. R. Zocchi Interaction between Human NK Cells and Bone Marrow Stromal Cells Induces NK Cell Triggering: Role of NKp30 and NKG2D Receptors J. Immunol., November 15, 2005; 175(10): 6352 - 6360. [Abstract] [Full Text] [PDF]