SEARCH:   Advanced

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ling, W. Articles by Finke, J. Search for Related Content PubMed PubMed Citation Articles by Ling, W. Articles by Finke, J. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 92 No. 4 (August 15), 1998: pp. 1334-1341 Impaired Activation of NFB in T Cells From a Subset of Renal Cell Carcinoma Patients Is Mediated by Inhibition of Phosphorylation and Degradation of the Inhibitor, IB Weijun Ling, Patricia Rayman, Robert Uzzo, Peter Clark, Hyung Jin Kim, Raymond Tubbs, Andrew Novick, Ronald Bukowski, Thomas Hamilton, and James Finke From the Departments of Immunology, Urology, Clinical Pathology, and Hematology-Oncology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH. Activation of the transcription factor NFB in peripheral blood T cells from patients with renal cell carcinoma (RCC) is compromised. This impaired signaling function results from a failure of RelA and c-Rel to translocate to the nucleus though normal levels of Rel proteins are present in the cytoplasm. We demonstrate here in a subset of RCC patients that the defect in NFB activation is attributable to the absence of phosphorylation and degradation of the inhibitor IB. In patient T cells there was no stimulus dependent decrease in the cytoplasmic level of IB. Coimmunoprecipitation studies showed that RelA was in complex with IB and was not released after stimulation. Moreover, the phosphorylated form of IB detected in normal T cells after activation is absent in patient T cells. Additional experiments showed that soluble products from RCCs (RCC-S) can reproduce the same phenotype in T cells from healthy individuals. Supernatant fluid from cultured explants of RCC, but not normal kidney, inhibited the stimulus dependent nuclear translocation of NFB without altering the cytoplasmic levels of RelA, c-Rel, and NFB1. Phosphorylation and degradation of IB was also blocked by RCC-S. The mechanistic similarities between patient-derived T cells and normal T cells cultured with RCC-S suggest that the tumor-derived products may be the primary mediators of impaired T-cell function in this tumor system. © 1998 by The American Society of Hematology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Bhattacharyya, D. Mandal, G. S. Sen, S. Pal, S. Banerjee, L. Lahiry, J. H. Finke, C. S. Tannenbaum, T. Das, and G. Sa Tumor-Induced Oxidative Stress Perturbs Nuclear Factor-{kappa}B Activity-Augmenting Tumor Necrosis Factor-{alpha}-Mediated T-Cell Death: Protection by Curcumin Cancer Res., January 1, 2007; 67(1): 362 - 370. [Abstract] [Full Text] [PDF] F. Chagnon, S. Tanguay, O. L. Ozdal, M. Guan, Z. Z. Ozen, J.-S. Ripeau, M. Chevrette, M. M. Elhilali, and L. A. Thompson-Snipes Potentiation of a Dendritic Cell Vaccine for Murine Renal Cell Carcinoma by CpG Oligonucleotides Clin. Cancer Res., February 1, 2005; 11(3): 1302 - 1311. [Abstract] [Full Text] [PDF] D. Kudo, P. Rayman, C. Horton, M. K. Cathcart, R. M. Bukowski, M. Thornton, C. Tannenbaum, and J. H. Finke Gangliosides Expressed by the Renal Cell Carcinoma Cell Line SK-RC-45 Are Involved in Tumor-induced Apoptosis of T Cells Cancer Res., April 1, 2003; 63(7): 1676 - 1683. [Abstract] [Full Text] [PDF] K.-J. Malmberg, R. Lenkei, M. Petersson, T. Ohlum, F. Ichihara, B. Glimelius, J.-E. Frodin, G. Masucci, and R. Kiessling A Short-Term Dietary Supplementation of High Doses of Vitamin E Increases T Helper 1 Cytokine Production in Patients with Advanced Colorectal Cancer Clin. Cancer Res., June 1, 2002; 8(6): 1772 - 1778. [Abstract] [Full Text] [PDF] A. G. S. Buggins, D. Milojkovic, M. J. Arno, N. C. Lea, G. J. Mufti, N. S. B. Thomas, and W. J. R. Hirst Microenvironment Produced by Acute Myeloid Leukemia Cells Prevents T Cell Activation and Proliferation by Inhibition of NF-{kappa}B, c-Myc, and pRb Pathways J. Immunol., November 15, 2001; 167(10): 6021 - 6030. [Abstract] [Full Text] [PDF] K.-J. Malmberg, V. Arulampalam, F. Ichihara, M. Petersson, K. Seki, T. Andersson, R. Lenkei, G. Masucci, S. Pettersson, and R. Kiessling Inhibition of Activated/Memory (CD45RO+) T Cells by Oxidative Stress Associated with Block of NF-{kappa}B Activation J. Immunol., September 1, 2001; 167(5): 2595 - 2601. [Abstract] [Full Text] [PDF] A. Gati, N. Guerra, J. Giron-Michel, B. Azzarone, E. Angevin, A. Moretta, S. Chouaib, and A. Caignard Tumor Cells Regulate the Lytic Activity of Tumor-specific Cytotoxic T Lymphocytes by Modulating the Inhibitory Natural Killer Receptor Function Cancer Res., April 1, 2001; 61(8): 3240 - 3244. [Abstract] [Full Text] S. Radoja, T. D. Rao, D. Hillman, and A. B. Frey Mice Bearing Late-Stage Tumors Have Normal Functional Systemic T Cell Responses In Vitro and In Vivo J. Immunol., March 1, 2000; 164(5): 2619 - 2628. [Abstract] [Full Text] [PDF] R. G. Uzzo, P. E. Clark, P. Rayman, T. Bloom, L. Rybicki, A. C. Novick, R. M. Bukowski, and J. H. Finke Alterations in NF{kappa}B Activation in T Lymphocytes of Patients With Renal Cell Carcinoma J Natl Cancer Inst, April 21, 1999; 91(8): 718 - 721. [Full Text] [PDF]

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 1998 by American Society of Hematology         Online ISSN: 1528-0020