| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
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.
This article has been cited by other articles:
|
|
 |
|
  A. Osterloh, A. Veit, A. Gessner, B. Fleischer, and M. Breloer Hsp60-mediated T cell stimulation is independent of TLR4 and IL-12 Int. Immunol., March 1, 2008; 20(3): 433 - 443. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kottke, L. Sanchez-Perez, R. M. Diaz, J. Thompson, H. Chong, K. Harrington, S. K. Calderwood, J. Pulido, N. Georgopoulos, P. Selby, et al. Induction of hsp70-Mediated Th17 Autoimmunity Can Be Exploited as Immunotherapy for Metastatic Prostate Cancer Cancer Res., December 15, 2007; 67(24): 11970 - 11979. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Chase, D. S. Wheeler, K. M. Lierl, V. S. Hughes, H. R. Wong, and K. Page Hsp72 Induces Inflammation and Regulates Cytokine Production in Airway Epithelium through a TLR4- and NF-{kappa}B-Dependent Mechanism J. Immunol., November 1, 2007; 179(9): 6318 - 6324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Sanchez-Perez, T. Kottke, G. A. Daniels, R. M. Diaz, J. Thompson, J. Pulido, A. Melcher, and R. G. Vile Killing of Normal Melanocytes, Combined with Heat Shock Protein 70 and CD40L Expression, Cures Large Established Melanomas J. Immunol., September 15, 2006; 177(6): 4168 - 4177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Stangl, A. Wortmann, U. Guertler, and G. Multhoff Control of Metastasized Pancreatic Carcinomas in SCID/Beige Mice with Human IL-2/TKD-Activated NK Cells J. Immunol., May 15, 2006; 176(10): 6270 - 6276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Sterman, A. Recio, A. Vachani, J. Sun, L. Cheung, P. DeLong, K. M. Amin, L. A. Litzky, J. M. Wilson, L. R. Kaiser, et al. Long-term Follow-up of Patients with Malignant Pleural Mesothelioma Receiving High-Dose Adenovirus Herpes Simplex Thymidine Kinase/Ganciclovir Suicide Gene Therapy Clin. Cancer Res., October 15, 2005; 11(20): 7444 - 7453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Massa, C. Melani, and M. P. Colombo Chaperon and Adjuvant Activity of hsp70: Different Natural Killer Requirement for Cross-Priming of Chaperoned and Bystander Antigens Cancer Res., September 1, 2005; 65(17): 7942 - 7949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Sanchez-Perez, T. Kottke, R. M. Diaz, A. Ahmed, J. Thompson, H. Chong, A. Melcher, S. Holmen, G. Daniels, and R. G. Vile Potent Selection of Antigen Loss Variants of B16 Melanoma following Inflammatory Killing of Melanocytes In vivo Cancer Res., March 1, 2005; 65(5): 2009 - 2017. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yamashita, W. Kamitani, H. Yanai, N. Ohtaki, Y. Watanabe, B.-J. Lee, S. Tsuji, K. Ikuta, and K. Tomonaga Persistent Borna Disease Virus Infection Confers Instability of HSP70 mRNA in Glial Cells during Heat Stress J. Virol., February 15, 2005; 79(4): 2033 - 2041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Berwin, Y. Delneste, R. V. Lovingood, S. R. Post, and S. V. Pizzo SREC-I, a Type F Scavenger Receptor, Is an Endocytic Receptor for Calreticulin J. Biol. Chem., December 3, 2004; 279(49): 51250 - 51257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Iordanskiy, Y. Zhao, L. Dubrovsky, T. Iordanskaya, M. Chen, D. Liang, and M. Bukrinsky Heat Shock Protein 70 Protects Cells from Cell Cycle Arrest and Apoptosis Induced by Human Immunodeficiency Virus Type 1 Viral Protein R J. Virol., September 15, 2004; 78(18): 9697 - 9704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Ren, R. Strube, X. Zhang, S.-Y. Chen, and X. F. Huang Potent Tumor-Specific Immunity Induced by an In vivo Heat Shock Protein-Suicide Gene-Based Tumor Vaccine Cancer Res., September 15, 2004; 64(18): 6645 - 6651. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Fagerlie, T. Koretsky, B. Torok-Storb, and G. C. Bagby Impaired Type I IFN-Induced Jak/STAT Signaling in FA-C Cells and Abnormal CD4+ Th Cell Subsets in Fancc-/- Mice J. Immunol., September 15, 2004; 173(6): 3863 - 3870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. SenGupta, P. J. Norris, T. J. Suscovich, M. Hassan-Zahraee, H. F. Moffett, A. Trocha, R. Draenert, P. J. R. Goulder, R. J. Binder, D. L. Levey, et al. Heat Shock Protein-Mediated Cross-Presentation of Exogenous HIV Antigen on HLA Class I and Class II J. Immunol., August 1, 2004; 173(3): 1987 - 1993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Massa, C. Guiducci, I. Arioli, M. Parenza, M. P. Colombo, and C. Melani Enhanced Efficacy of Tumor Cell Vaccines Transfected with Secretable hsp70 Cancer Res., February 15, 2004; 64(4): 1502 - 1508. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Dressel, C. Grzeszik, M. Kreiss, D. Lindemann, T. Herrmann, L. Walter, and E. Gunther Differential Effect of Acute and Permanent Heat Shock Protein 70 Overexpression in Tumor Cells on Lysability by Cytotoxic T Lymphocytes Cancer Res., December 1, 2003; 63(23): 8212 - 8220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Crittenden, M. Gough, K. Harrington, K. Olivier, J. Thompson, and R. G. Vile Expression of Inflammatory Chemokines Combined with Local Tumor Destruction Enhances Tumor Regression and Long-term Immunity Cancer Res., September 1, 2003; 63(17): 5505 - 5512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Schirmbeck, N. Fissolo, P. Chaplin, and J. Reimann Enhanced Priming of Multispecific, Murine CD8+ T Cell Responses by DNA Vaccines Expressing Stress Protein-Binding Polytope Peptides J. Immunol., August 1, 2003; 171(3): 1240 - 1246. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zeng, H. Feng, M. W. Graner, and E. Katsanis Tumor-derived, chaperone-rich cell lysate activates dendritic cells and elicits potent antitumor immunity Blood, June 1, 2003; 101(11): 4485 - 4491. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Miura, K. Morris, S. Ryan, J. L. Cook, and J. M. Routes Adenovirus E1A, Not Human Papillomavirus E7, Sensitizes Tumor Cells to Lysis by Macrophages Through Nitric Oxide- and TNF-{alpha}-Dependent Mechanisms Despite Up-Regulation of 70-kDa Heat Shock Protein J. Immunol., April 15, 2003; 170(8): 4119 - 4126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Vanden Berghe, M. Kalai, G. van Loo, W. Declercq, and P. Vandenabeele Disruption of HSP90 Function Reverts Tumor Necrosis Factor-induced Necrosis to Apoptosis J. Biol. Chem., February 14, 2003; 278(8): 5622 - 5629. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Baker-LePain, M. Sarzotti, T. A. Fields, C.-Y. Li, and C. V. Nicchitta GRP94 (gp96) and GRP94 N-Terminal Geldanamycin Binding Domain Elicit Tissue Nonrestricted Tumor Suppression J. Exp. Med., December 2, 2002; 196(11): 1447 - 1459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Noessner, R. Gastpar, V. Milani, A. Brandl, P. J. S. Hutzler, M. C. Kuppner, M. Roos, E. Kremmer, A. Asea, S. K. Calderwood, et al. Tumor-Derived Heat Shock Protein 70 Peptide Complexes Are Cross-Presented by Human Dendritic Cells J. Immunol., November 15, 2002; 169(10): 5424 - 5432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-M. Hu, H. Winter, J. Ma, M. Croft, W. J. Urba, and B. A. Fox CD28, TNF Receptor, and IL-12 Are Critical for CD4-Independent Cross-Priming of Therapeutic Antitumor CD8+ T Cells J. Immunol., November 1, 2002; 169(9): 4897 - 4904. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-H. Rha, C. Taube, A. Haczku, A. Joetham, K. Takeda, C. Duez, M. Siegel, M. K. Aydintug, W. K. Born, A. Dakhama, et al. Effect of Microbial Heat Shock Proteins on Airway Inflammation and Hyperresponsiveness J. Immunol., November 1, 2002; 169(9): 5300 - 5307. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W van Eden, R van der Zee, P van Kooten, S E Berlo, P M Cobelens, A Kavelaars, C J Heijnen, B Prakken, S Roord, and S Albani Balancing the immune system: Th1 and Th2 Ann Rheum Dis, November 1, 2002; 61(90002): ii25 - 28. [Full Text] [PDF]
|
|
|
|
|
|
E. Linardakis, A. Bateman, V. Phan, A. Ahmed, M. Gough, K. Olivier, R. Kennedy, F. Errington, K. J. Harrington, A. Melcher, et al. Enhancing the Efficacy of a Weak Allogeneic Melanoma Vaccine by Viral Fusogenic Membrane Glycoprotein-mediated Tumor Cell-Tumor Cell Fusion Cancer Res., October 1, 2002; 62(19): 5495 - 5504. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Liu, A. M. DeFilippo, and Z. Li Overcoming Immune Tolerance to Cancer by Heat Shock Protein Vaccines Mol. Cancer Ther., October 1, 2002; 1(12): 1147 - 1151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. C. Kregel Molecular Biology of Thermoregulation: Invited Review: Heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance J Appl Physiol, May 1, 2002; 92(5): 2177 - 2186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Asea, M. Rehli, E. Kabingu, J. A. Boch, O. Bare, P. E. Auron, M. A. Stevenson, and S. K. Calderwood Novel Signal Transduction Pathway Utilized by Extracellular HSP70. ROLE OF Toll-LIKE RECEPTOR (TLR) 2 AND TLR4 J. Biol. Chem., April 19, 2002; 277(17): 15028 - 15034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Schnurr, C. Scholz, S. Rothenfusser, P. Galambos, M. Dauer, J. Robe, S. Endres, and A. Eigler Apoptotic Pancreatic Tumor Cells Are Superior to Cell Lysates in Promoting Cross-Priming of Cytotoxic T Cells and Activate NK and {gamma}{delta} T Cells Cancer Res., April 1, 2002; 62(8): 2347 - 2352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Strome, S. Voss, R. Wilcox, T. L. Wakefield, K. Tamada, D. Flies, A. Chapoval, J. Lu, J. L. Kasperbauer, D. Padley, et al. Strategies for Antigen Loading of Dendritic Cells to Enhance the Antitumor Immune Response Cancer Res., March 1, 2002; 62(6): 1884 - 1889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kammerer, D. Stober, P. Riedl, C. Oehninger, R. Schirmbeck, and J. Reimann Noncovalent Association with Stress Protein Facilitates Cross-Priming of CD8+ T Cells to Tumor Cell Antigens by Dendritic Cells J. Immunol., January 1, 2002; 168(1): 108 - 117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Fortin, J. Lagace, and H.-M. Therien Trafficking of Surface-linked and Encapsulated Liposomal Antigens in Macrophages: an Immunocytochemical Study J. Histochem. Cytochem., November 1, 2001; 49(11): 1407 - 1420. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kotera, K. Shimizu, and J. J. Mule Comparative Analysis of Necrotic and Apoptotic Tumor Cells As a Source of Antigen(s) in Dendritic Cell-based Immunization Cancer Res., November 1, 2001; 61(22): 8105 - 8109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Gough, A. A. Melcher, A. Ahmed, M. R. Crittenden, D. S. Riddle, E. Linardakis, A. N. Ruchatz, L. M. Emiliusen, and R. G. Vile Macrophages Orchestrate the Immune Response to Tumor Cell Death Cancer Res., October 1, 2001; 61(19): 7240 - 7247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Feng, Y. Zeng, L. Whitesell, and E. Katsanis Stressed apoptotic tumor cells express heat shock proteins and elicit tumor-specific immunity Blood, June 1, 2001; 97(11): 3505 - 3512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
