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Prepublished online as a Blood First Edition Paper on July 25, 2002; DOI 10.1182/blood-2002-05-1389. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-05-1389v1 100/12/4108    most recent 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 Feng, H. Articles by Katsanis, E. Search for Related Content PubMed PubMed Citation Articles by Feng, H. Articles by Katsanis, E. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 December 2002, Vol. 100, No. 12, pp. 4108-4115 IMMUNOBIOLOGY Stressed apoptotic tumor cells stimulate dendritic cells and induce specific cytotoxic T cells Hanping Feng, Yi Zeng, Michael W. Graner, and Emmanuel Katsanis From the Department of Pediatrics, Steele Memorial Children's Research Center, University of Arizona, Tucson. We have previously reported that stressed apoptotic tumor cells are more immunogenic in vivo than nonstressed ones. Using confocal microscopy we have confirmed our previous observation that heat-stressed apoptotic 12B1-D1 leukemia cells (BCR-ABL+) express HSP60 and HSP72 on their surface. To explore how the immune system distinguishes stressed from nonstressed apoptotic tumor cells, we analyzed the responses of dendritic cells to these 2 types of apoptotic cells. We found that nonstressed and heat-stressed apoptotic 12B1-D1 cells were taken up by dendritic cells in a comparable fashion. However, when stressed apoptotic 12B1-D1 cells were coincubated with immature dendritic cells for 24 hours, this resulted in greater up-regulation of costimulatory molecules (CD40, CD80, and CD86) on the surface of dendritic cells. Moreover, stressed apoptotic 12B1-D1 cells were more effective in stimulating dendritic cells to secrete interleukin-12 (IL-12) and in enhancing their immunostimulatory functions in mixed leukocyte reactions. Furthermore, we demonstrated that immunization of mice with stressed apoptotic 12B1-D1 cells induced the secretion of T helper-1 (TH1) profile of cytokines by spleen cells. Splenocytes from mice immunized with stressed apoptotic cells, but not nonstressed ones, were capable of lysing 12B1-D1 and the parental 12B1 line, but not a B-cell leukemia line, A20. Our data indicate that stressed apoptotic tumor cells are capable of providing the necessary danger signals, likely through increased surface expression of heat shock proteins (HSPs), resulting in activation/maturation of dendritic cells and, ultimately, the generation of potent antitumor T-cell responses. © 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. Koido, E. Hara, S. Homma, M. Mitsunaga, A. Takahara, E. Nagasaki, H. Kawahara, M. Watanabe, Y. Toyama, S. Yanagisawa, et al. Synergistic Induction of Antigen-Specific CTL by Fusions of TLR-Stimulated Dendritic Cells and Heat-Stressed Tumor Cells J. Immunol., October 1, 2007; 179(7): 4874 - 4883. [Abstract] [Full Text] [PDF] L. Negroni, M. Samson, J.-M. Guigonis, B. Rossi, V. Pierrefite-Carle, and C. 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