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 Ratta, M. Articles by Lemoli, R. M. Search for Related Content PubMed PubMed Citation Articles by Ratta, M. Articles by Lemoli, R. M. Related Collections Immunobiology Neoplasia Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 July 2002, Vol. 100, No. 1, pp. 230-237 NEOPLASIA Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6 Marina Ratta, Francesco Fagnoni, Antonio Curti, Rosanna Vescovini, Paolo Sansoni, Barbara Oliviero, Miriam Fogli, Elisa Ferri, Gioacchino Robustelli Della Cuna, Sante Tura, Michele Baccarani, and Roberto M. Lemoli From the Institute of Hematology and Medical Oncology, "Lorenzo e Ariosto Seràgnoli," University of Bologna; the Department of Internal Medicine, University of Parma; and S. Maugeri Foundation, Instituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Clinica del Lavoro e della Riabilitazione, Scientific Institute of Pavia, Italy. We studied concentration, phenotype, and function of peripheral blood (PB) dendritic cells (DCs) from patients with multiple myeloma (MM). The absolute number of circulating precursors of myeloid and plasmacytoid DCs was significantly lower in MM patients than in healthy subjects. After maturation, PBDCs from MM patients showed significantly lower expression of HLA-DR, CD40, and CD80 antigens and impaired induction of allogeneic T-cell proliferation compared with controls. Remarkably, they were not capable of presenting the patient-specific tumor idiotype to autologous T cells. Conversely, DCs generated in vitro from CD14+ monocytes from the same patients, and PBDCs freshly isolated from healthy donors efficiently stimulated allogeneic and autologous T cells. To clarify the mechanism of PBDC deficiency in MM, we investigated the effects of the main plasma cell growth factor, interleukin-6 (IL-6), on the development of DCs from CD34+ cells. IL-6 inhibited the colony growth of CD34+ DC progenitors and switched the commitment of CD34+ cells from DCs to CD14+ CD1a CD86CD80 CD40±HLA-DR ± monocytic cells exerting potent phagocytic activity but no antigen-presentation capacity. This effect was reversed by anti-IL-6 antibodies. Growing CD34+ cells in the presence of autologous serum (without IL-6) also suppressed the development of functional DCs. This study demonstrates that PBDCs from MM patients are functionally defective, partially because of IL-6-mediated inhibition of development. This brings into question the advisability of using PBDCs as antigen carriers for immunotherapy trials in MM. The results also suggest a novel mechanism whereby myeloma cells escape immune recognition. © 2002 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. Mathew, K. L. Bauer, A. Fischoeder, N. Bhardwaj, and S. J. Oliver The Anergic State in Sarcoidosis Is Associated with Diminished Dendritic Cell Function J. Immunol., July 1, 2008; 181(1): 746 - 755. [Abstract] [Full Text] [PDF] M. Martin-Ayuso, J. Almeida, M. Perez-Andres, R. Cuello, J. Galende, M. I. Gonzalez-Fraile, G. Martin-Nunez, F. Ortega, M. J. Rodriguez, J. F. San Miguel, et al. Peripheral Blood Dendritic Cell Subsets from Patients with Monoclonal Gammopathies Show an Abnormal Distribution and Are Functionally Impaired Oncologist, January 1, 2008; 13(1): 82 - 92. [Abstract] [Full Text] [PDF] S. Yu, C. Liu, K. Su, J. Wang, Y. Liu, L. Zhang, C. Li, Y. Cong, R. Kimberly, W. E. Grizzle, et al. Tumor Exosomes Inhibit Differentiation of Bone Marrow Dendritic Cells J. Immunol., June 1, 2007; 178(11): 6867 - 6875. [Abstract] [Full Text] [PDF] F. v. Rhee Idiotype Vaccination Strategies in Myeloma: How to Overcome a Dysfunctional Immune System Clin. Cancer Res., March 1, 2007; 13(5): 1353 - 1355. [Full Text] [PDF] S. Wang, S. Hong, J. Yang, J. Qian, X. Zhang, E. Shpall, L. W. Kwak, and Q. Yi Optimizing immunotherapy in multiple myeloma: restoring the function of patients' monocyte-derived dendritic cells by inhibiting p38 or activating MEK/ERK MAPK and neutralizing interleukin-6 in progenitor cells Blood, December 15, 2006; 108(13): 4071 - 4077. [Abstract] [Full Text] [PDF] G. Bellone, A. Carbone, C. Smirne, T. Scirelli, A. Buffolino, A. Novarino, A. Stacchini, O. Bertetto, G. Palestro, C. Sorio, et al. Cooperative induction of a tolerogenic dendritic cell phenotype by cytokines secreted by pancreatic carcinoma cells. J. Immunol., September 1, 2006; 177(5): 3448 - 3460. [Abstract] [Full Text] [PDF] S. Rutella, G. Bonanno, A. Procoli, A. Mariotti, D. G. de Ritis, A. Curti, S. Danese, G. Pessina, S. Pandolfi, F. Natoni, et al. Hepatocyte growth factor favors monocyte differentiation into regulatory interleukin (IL)-10++IL-12low/neg accessory cells with dendritic-cell features Blood, July 1, 2006; 108(1): 218 - 227. [Abstract] [Full Text] [PDF] J. P. J. J. Hegmans, A. Hemmes, H. Hammad, L. Boon, H. C. Hoogsteden, and B. N. Lambrecht Mesothelioma environment comprises cytokines and T-regulatory cells that suppress immune responses Eur. Respir. J., June 1, 2006; 27(6): 1086 - 1095. [Abstract] [Full Text] [PDF] S. Appel, A. Bringmann, F. Grunebach, M. M. Weck, J. Bauer, and P. Brossart Epithelial-specific transcription factor ESE-3 is involved in the development of monocyte-derived DCs Blood, April 15, 2006; 107(8): 3265 - 3270. [Abstract] [Full Text] [PDF] S. Wang, J. Yang, J. Qian, M. Wezeman, L. W. Kwak, and Q. Yi Tumor evasion of the immune system: inhibiting p38 MAPK signaling restores the function of dendritic cells in multiple myeloma Blood, March 15, 2006; 107(6): 2432 - 2439. [Abstract] [Full Text] [PDF] A. Jalili, S. Ozaki, T. Hara, H. Shibata, T. Hashimoto, M. Abe, Y. Nishioka, and T. Matsumoto Induction of HM1.24 peptide-specific cytotoxic T lymphocytes by using peripheral-blood stem-cell harvests in patients with multiple myeloma Blood, November 15, 2005; 106(10): 3538 - 3545. [Abstract] [Full Text] [PDF] Y. Nefedova, S. Nagaraj, A. Rosenbauer, C. Muro-Cacho, S. M. Sebti, and D. I. Gabrilovich Regulation of Dendritic Cell Differentiation and Antitumor Immune Response in Cancer by Pharmacologic-Selective Inhibition of the Janus-Activated Kinase 2/Signal Transducers and Activators of Transcription 3 Pathway Cancer Res., October 15, 2005; 65(20): 9525 - 9535. [Abstract] [Full Text] [PDF] I. L. Tourkova, G. V. Shurin, G. S. Chatta, L. Perez, J. Finke, T. L. Whiteside, S. Ferrone, and M. R. Shurin Restoration by IL-15 of MHC Class I Antigen-Processing Machinery in Human Dendritic Cells Inhibited by Tumor-Derived Gangliosides J. Immunol., September 1, 2005; 175(5): 3045 - 3052. [Abstract] [Full Text] [PDF] L. Alberti, T. Bachelot, A. Duc, C. Biota, and J. Y. Blay A Spliced Isoform of Interleukin 6 mRNA Produced by Renal Cell Carcinoma Encodes for an Interleukin 6 Inhibitor Cancer Res., January 1, 2005; 65(1): 2 - 5. [Abstract] [Full Text] [PDF] S. Beckebaum, X. Zhang, X. Chen, Z. Yu, A. Frilling, G. Dworacki, H. Grosse-Wilde, C. E. Broelsch, G. Gerken, and V. R. Cicinnati Increased Levels of Interleukin-10 in Serum from Patients with Hepatocellular Carcinoma Correlate with Profound Numerical Deficiencies and Immature Phenotype of Circulating Dendritic Cell Subsets Clin. Cancer Res., November 1, 2004; 10(21): 7260 - 7269. [Abstract] [Full Text] [PDF] S.-J. Park, T. Nakagawa, H. Kitamura, T. Atsumi, H. Kamon, S.-i. Sawa, D. Kamimura, N. Ueda, Y. Iwakura, K. Ishihara, et al. IL-6 Regulates In Vivo Dendritic Cell Differentiation through STAT3 Activation J. Immunol., September 15, 2004; 173(6): 3844 - 3854. [Abstract] [Full Text] [PDF] A. Encabo, P. Solves, E. Mateu, P. Sepulveda, F. Carbonell-Uberos, and M. D. Minana Selective Generation of Different Dendritic Cell Precursors from CD34+ Cells by Interleukin-6 and Interleukin-3 Stem Cells, September 1, 2004; 22(5): 725 - 740. [Abstract] [Full Text] [PDF] F. F. Fagnoni, B. Oliviero, G. Giorgiani, P. De Stefano, A. Deho, C. Zibera, N. Gibelli, R. Maccario, G. Da Prada, M. Zecca, et al. Reconstitution dynamics of plasmacytoid and myeloid dendritic cell precursors after allogeneic myeloablative hematopoietic stem cell transplantation Blood, July 1, 2004; 104(1): 281 - 289. [Abstract] [Full Text] [PDF] J. I. Bleier, V. G. Pillarisetty, A. B. Shah, and R. P. DeMatteo Increased and Long-Term Generation of Dendritic Cells with Reduced Function from IL-6-Deficient Bone Marrow J. Immunol., June 15, 2004; 172(12): 7408 - 7416. [Abstract] [Full Text] [PDF] F. Dayyani, A. Joeinig, L. Ziegler-Heitbrock, R. Schmidmaier, C. Straka, B. Emmerich, and G. Meinhardt Autologous stem-cell transplantation restores the functional properties of CD14+CD16+ monocytes in patients with myeloma and lymphoma J. Leukoc. Biol., February 1, 2004; 75(2): 207 - 213. [Abstract] [Full Text] [PDF] A. Curti, E. Ferri, S. Pandolfi, A. Isidori, R. M. Lemoli, M. Dauer, K. Schad, J. Herten, S. Endres, and A. Eigler Dendritic Cell Differentiation J. Immunol., January 1, 2004; 172(1): 3 - 4. [Full Text] [PDF] T. Hayashi, T. Hideshima, M. Akiyama, N. Raje, P. Richardson, D. Chauhan, and K. C. Anderson Ex vivo induction of multiple myeloma-specific cytotoxic T lymphocytes Blood, August 15, 2003; 102(4): 1435 - 1442. [Abstract] [Full Text] [PDF] E. Orsini, A. Guarini, S. Chiaretti, F. R. Mauro, and R. Foa The Circulating Dendritic Cell Compartment in Patients with Chronic Lymphocytic Leukemia Is Severely Defective and Unable to Stimulate an Effective T-Cell Response Cancer Res., August 1, 2003; 63(15): 4497 - 4506. [Abstract] [Full Text] [PDF] A. K. De, K. Laudanski, and C. L. Miller-Graziano Failure of Monocytes of Trauma Patients to Convert to Immature Dendritic Cells is Related to Preferential Macrophage-Colony-Stimulating Factor-Driven Macrophage Differentiation J. Immunol., June 15, 2003; 170(12): 6355 - 6362. [Abstract] [Full Text] [PDF] J. Xie, Y. Wang, M. E. Freeman III, B. Barlogie, and Q. Yi beta 2-Microglobulin as a negative regulator of the immune system: high concentrations of the protein inhibit in vitro generation of functional dendritic cells Blood, May 15, 2003; 101(10): 4005 - 4012. [Abstract] [Full Text] [PDF] M. V. Dhodapkar, J. Krasovsky, and K. Olson T cells from the tumor microenvironment of patients with progressive myeloma can generate strong, tumor-specific cytolytic responses to autologous, tumor-loaded dendritic cells PNAS, October 1, 2002; 99(20): 13009 - 13013. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020