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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cignetti, A. Articles by Caligaris-Cappio, F. Search for Related Content PubMed PubMed Citation Articles by Cignetti, A. Articles by Caligaris-Cappio, F.

Leukemia-Derived Immature Dendritic Cells Differentiate into Functionally Competent Mature Dendritic Cells That Efficiently Stimulate T Cell Responses¹

Alessandro Cignetti^2,*, Antonella Vallario^*,, Ilaria Roato^*, Paola Circosta^*, Bernardino Allione, Laura Casorzo, Paolo Ghia^*, and Federico Caligaris-Cappio^3,*,

^* Laboratory of Cancer Immunology, Institute for Cancer Research and Treatment, Department of Oncological Sciences, University of Torino Medical School, and Unit of Pathology, Institute for Cancer Research and Treatment, Candiolo, Italy; and Division of Hematology, Azienda Ospedaliera Santissimi. Antonio e Biagio, Alessandria, Italy

Primary acute myeloid leukemia cells can be induced to differentiate into dendritic cells (DC). In the presence of GM-CSF, TNF-, and/or IL-4, leukemia-derived DC are obtained that display features of immature DC (i-DC). The aim of this study was to determine whether i-DC of leukemic origin could be further differentiated into mature DC (m-DC) and to evaluate the possibility that leukemic m-DC could be effective in vivo as a tumor vaccine. Using CD40L as maturating agent, we show that leukemic i-DC can differentiate into cells that fulfill the phenotypic criteria of m-DC and, compared with normal counterparts, are functionally competent in vitro in terms of: 1) production of cytokines that support T cell activation and proliferation and drive Th1 polarization; 2) generation of autologous CD8⁺ CTLs and CD4⁺ T cells that are MHC-restricted and leukemia-specific; 3) migration from tissues to lymph nodes; 4) amplification of Ag presentation by monocyte attraction; 5) attraction of naive/resting and activated T cells. Irradiation of leukemic i-DC after CD40L stimulation did not affect their differentiating and functional capacity. Our data indicate that acute myeloid leukemia cells can fully differentiate into functionally competent m-DC and lay the ground for testing their efficacy as a tumor vaccine.

This article has been cited by other articles:

				K. Schmidt, K. Seeger, C. Scheibenbogen, R. Bender, M. Abdulla, S. Sussmilch, A. Salama, and A. Moldenhauer Histone deacetylase inhibition improves differentiation of dendritic cells from leukemic blasts of patients with TEL/AML1-positive acute lymphoblastic leukemia J. Leukoc. Biol., March 1, 2009; 85(3): 563 - 573. [Abstract] [Full Text] [PDF]

				E. L.J.M. Smits, Z. N. Berneman, and V. F.I. Van Tendeloo Immunotherapy of Acute Myeloid Leukemia: Current Approaches Oncologist, March 1, 2009; 14(3): 240 - 252. [Abstract] [Full Text] [PDF]

				Q. Sun, C. T. Kong, F. P. Huang, and L. C. Chan Aberrant dendritic cell differentiation initiated by the Mll-Een fusion gene does not require leukemic transformation J. Leukoc. Biol., January 1, 2008; 83(1): 173 - 180. [Abstract] [Full Text] [PDF]

				F. Carnevale-Schianca, A. Cignetti, A. Capaldi, K. Vitaggio, A. Vallario, A. Ricchiardi, E. Sperti, R. Ferraris, M. Gatti, G. Grignani, et al. Allogeneic nonmyeloablative hematopoietic cell transplantation in metastatic colon cancer: tumor-specific T cells directed to a tumor-associated antigen are generated in vivo during GVHD Blood, May 1, 2006; 107(9): 3795 - 3803. [Abstract] [Full Text] [PDF]