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*
Imperial Cancer Research Fund Laboratory of Molecular Therapy, Imperial Cancer Research Fund Oncology Unit, Imperial College of Science and Medicine, Hammersmith Hospital, London, United Kingdom;
Molecular Medicine Program, Mayo Clinic, Rochester, MN 55905;
Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy; and
Department of Experimental Medicine and Pathology, Second Chair of Pathology, University of Rome La Sapienza, Rome, Italy
Previously, we reported that killing tumor cells in vivo with the
HSV thymidine kinase/ganciclovir system generates potent antitumor
immunity, determined in part by the mechanism by which the cells die
and by the levels of inducible heat shock protein (hsp) expression
induced during the process of cell death. Here, we show that induction
of hsp70 expression induces an infiltrate of T cells, macrophages, and
predominantly dendritic cells (DCs) into the tumors as well as an
intratumoral profile of Th1 cytokine expression (IFN-
, TNF-
, and
IL-12) and enhances immunogenicity via a T cell-mediated mechanism. In
addition, the protection conferred by hsp70 is both tumor and cell
specific. We also demonstrate that hsp70 targets immature APC to make
them significantly more able to capture Ags. This is likely to optimize
cross-priming of the infiltrating APC with tumor Ags, which are
simultaneously being released by the dying cells. In addition, using an
Myc epitope-tagged hsp70 expression vector, we present evidence that
hsp70 released from dying tumor cells is taken up directly into DCs and
may, therefore, be involved in direct chaperoning of Ags into DCs.
Taken together, our data suggest that hsp70 induction serves to signal
the immune system of the presence of an immunologically relevant
(dangerous) situation against which an immune reaction should be
raised.
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|
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|
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|
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|
|
|
|
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|
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|
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|
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|
|
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|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
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S. Liu, Y. Yu, M. Zhang, W. Wang, and X. Cao The Involvement of TNF-{{alpha}}-Related Apoptosis-Inducing Ligand in the Enhanced Cytotoxicity of IFN-{{beta}}-Stimulated Human Dendritic Cells to Tumor Cells J. Immunol., May 1, 2001; 166(9): 5407 - 5415. [Abstract] [Full Text] [PDF]
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J. R. Kanwar, R. K. Kanwar, S. Pandey, L.-M. Ching, and G. W. Krissansen Vascular Attack by 5,6-Dimethylxanthenone-4-acetic Acid Combined with B7.1 (CD80)-mediated Immunotherapy Overcomes Immune Resistance and Leads to the Eradication of Large Tumors and Multiple Tumor Foci Cancer Res., March 1, 2001; 61(5): 1948 - 1956. [Abstract] [Full Text]
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D. M. Hall, L. Xu, V. J. Drake, L. W. Oberley, T. D. Oberley, P. L. Moseley, and K. C. Kregel Aging reduces adaptive capacity and stress protein expression in the liver after heat stress J Appl Physiol, August 1, 2000; 89(2): 749 - 759. [Abstract] [Full Text] [PDF]
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M. Lanuti, S. Rudginsky, S. D. Force, E. S. Lambright, W. M. Siders, M. Y. Chang, K. M. Amin, L. R. Kaiser, R. K. Scheule, and S. M. Albelda Cationic Lipid:Bacterial DNA Complexes Elicit Adaptive Cellular Immunity in Murine Intraperitoneal Tumor Models Cancer Res., June 1, 2000; 60(11): 2955 - 2963. [Abstract] [Full Text] [PDF]
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A. Bateman, F. Bullough, S. Murphy, L. Emiliusen, D. Lavillette, F.-L. Cosset, R. Cattaneo, S. J. Russell, and R. G. Vile Fusogenic Membrane Glycoproteins As a Novel Class of Genes for the Local and Immune-mediated Control of Tumor Growth Cancer Res., March 1, 2000; 60(6): 1492 - 1497. [Abstract] [Full Text]
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B. Sauter, M. L. Albert, L. Francisco, M. Larsson, S. Somersan, and N. Bhardwaj Consequences of Cell Death: Exposure to Necrotic Tumor Cells, but Not Primary Tissue Cells or Apoptotic Cells, Induces the Maturation of Immunostimulatory Dendritic Cells J. Exp. Med., February 7, 2000; 191(3): 423 - 434. [Abstract] [Full Text] [PDF]
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 J. C. Morris Enzyme/Prodrug-Based Tumor Vaccination: All Politics (and Immunity) Are Local J Natl Cancer Inst, December 1, 1999; 91(23): 1986 - 1989. [Full Text] [PDF]
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K. Bellmann, V. Burkart, J. Bruckhoff, H. Kolb, and J. Landry p38-dependent Enhancement of Cytokine-induced Nitric-oxide Synthase Gene Expression by Heat Shock Protein 70 J. Biol. Chem., June 9, 2000; 275(24): 18172 - 18179. [Abstract] [Full Text] [PDF]
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F. Le Naour, L. Hohenkirk, A. Grolleau, D. E. Misek, P. Lescure, J. D. Geiger, S. Hanash, and L. Beretta Profiling Changes in Gene Expression during Differentiation and Maturation of Monocyte-derived Dendritic Cells Using Both Oligonucleotide Microarrays and Proteomics J. Biol. Chem., May 18, 2001; 276(21): 17920 - 17931. [Abstract] [Full Text] [PDF]
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B. Berwin, R. C. Reed, and C. V. Nicchitta Virally Induced Lytic Cell Death Elicits the Release of Immunogenic GRP94/gp96 J. Biol. Chem., June 8, 2001; 276(24): 21083 - 21088. [Abstract] [Full Text] [PDF]
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