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Autoimmune Diseases
Volume 2012, Article ID 486069, 10 pages
http://dx.doi.org/10.1155/2012/486069
Review Article

Heat Shock Proteins, Autoimmunity, and Cancer Treatment

Division of Molecular and Cellular Biology, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Avenue, Boston, MA 02215, USA

Received 16 July 2012; Accepted 27 August 2012

Academic Editor: Kamal D. Moudgil

Copyright © 2012 Stuart K. Calderwood et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. Nikolich-Žugich, M. K. Slifka, and I. Messaoudi, “The many important facets of T-cell repertoire diversity,” Nature Reviews Immunology, vol. 4, no. 2, pp. 123–132, 2004. View at Google Scholar · View at Scopus
  2. L. S. K. Walker and A. K. Abbas, “The enemy within: keeping self-reactive T cells at bay in the periphery,” Nature Reviews Immunology, vol. 2, no. 1, pp. 11–19, 2002. View at Google Scholar · View at Scopus
  3. D. Pardoll, “Does the immune system see tumors as foreign or self?” Annual Review of Immunology, vol. 21, pp. 807–839, 2003. View at Publisher · View at Google Scholar · View at Scopus
  4. P. K. Srivastava and L. J. Old, “Individually distinc transplantation antigens of chemically induced mouse tumors,” Immunology Today, vol. 9, no. 3, pp. 78–83, 1988. View at Google Scholar · View at Scopus
  5. P. Moller and G. J. Hammerling, “The role of surface HLA-A,B,C molecules in tumour immunity,” Cancer Surveys, vol. 13, pp. 101–127, 1992. View at Google Scholar · View at Scopus
  6. S. Chouaib, J. Thiery, A. Gati et al., “Tumor escape from killing: role of killer inhibitory receptors and acquisition of tumor resistance to cell death,” Tissue Antigens, vol. 60, no. 4, pp. 273–281, 2002. View at Publisher · View at Google Scholar · View at Scopus
  7. L. A. Pekarek, B. A. Starr, A. Y. Toledano, and H. Schreiber, “Inhibition of tumor growth by elimination of granulocytes,” Journal of Experimental Medicine, vol. 181, no. 1, pp. 435–440, 1995. View at Publisher · View at Google Scholar · View at Scopus
  8. M. Terabe, J. Swann, E. Ambrosino et al., “A nonclassical non-Vα14Jα18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance,” Journal of Experimental Medicine, vol. 202, no. 12, pp. 1627–1633, 2005. View at Publisher · View at Google Scholar · View at Scopus
  9. A. Mantovani, P. Allavena, A. Sica, and F. Balkwill, “Cancer-related inflammation,” Nature, vol. 454, no. 7203, pp. 436–444, 2008. View at Publisher · View at Google Scholar · View at Scopus
  10. I. Marigo, L. Dolcetti, P. Serafini, P. Zanovello, and V. Bronte, “Tumor-induced tolerance and immune suppression by myeloid derived suppressor cells,” Immunological Reviews, vol. 222, no. 1, pp. 162–179, 2008. View at Publisher · View at Google Scholar · View at Scopus
  11. S. Liu, J. Lachapelle, S. Leung et al., “CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer,” Breast Cancer Research, vol. 14, no. 2, article R48, 2012. View at Google Scholar
  12. J. Galon, A. Costes, F. Sanchez-Cabo et al., “Type, density, and location of immune cells within human colorectal tumors predict clinical outcome,” Science, vol. 313, no. 5795, pp. 1960–1964, 2006. View at Publisher · View at Google Scholar · View at Scopus
  13. W. H. Fridman, F. Pages, C. Sautes-Fridman, and J. Galon, “The immune contexture in human tumours: impact on clinical outcome,” Nature Reviews Cancer, vol. 12, pp. 298–306, 2011. View at Google Scholar
  14. M. Beyer, B. Schumak, M. R. Weihrauch et al., “In vivo expansion of naive CD4+CD25high FOXP3+ regulatory T cells in patients with colorectal carcinoma after IL-2 administration,” PLoS ONE, vol. 7, Article ID e30422, 2012. View at Google Scholar
  15. A. Schmidt, N. Oberle, and P H. Krammer, “Molecular mechanisms of tregmediated T cell suppression,” Frontiers in Immunology, vol. 3, p. 51, 2012. View at Publisher · View at Google Scholar
  16. J. E. Visvader, “Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis,” Genes and Development, vol. 23, no. 22, pp. 2563–2577, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. T. Schatton and M. H. Frank, “Antitumor immunity and cancer stem cells,” Annals of the New York Academy of Sciences, vol. 1176, pp. 154–169, 2009. View at Publisher · View at Google Scholar · View at Scopus
  18. M. Kraman, P. J. Bambrough, J. N. Arnold et al., “Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-α,” Science, vol. 330, no. 6005, pp. 827–830, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. G. C. Li and Z. Werb, “Correlation between synthesis of heat shock proteins and development of thermotolerance in Chinese hamster fibroblasts,” Proceedings of the National Academy of Sciences of the United States of America, vol. 79, no. 10, pp. 3218–3222, 1982. View at Google Scholar · View at Scopus
  20. S. K. Calderwood, Y. Xie, X. Wang et al., “Signal transduction pathways leading to heat shock transcription,” Sign Transduct Insights, vol. 2, pp. 13–24, 2010. View at Google Scholar
  21. R. J. Ellis, “Protein misassembly: macromolecular crowding and molecular chaperones,” Advances in Experimental Medicine and Biology, vol. 594, pp. 1–13, 2007. View at Publisher · View at Google Scholar · View at Scopus
  22. M. P. Mayer and B. Bukau, “Hsp70 chaperones: cellular functions and molecular mechanism,” Cellular and Molecular Life Sciences, vol. 62, no. 6, pp. 670–684, 2005. View at Publisher · View at Google Scholar · View at Scopus
  23. E. A. Craig, “The stress response: changes in eukaryotic gene expression in response to environmental stress,” Science, vol. 230, pp. 800–801, 1985. View at Google Scholar
  24. W. van Eden, “Heat-shock proteins as immunogenic bacterial antigens with the potential to induce and regulate autoimmune arthritis,” Immunological Reviews, no. 121, pp. 5–28, 1991. View at Google Scholar · View at Scopus
  25. W. Van Eden, G. Wick, S. Albani, and I. Cohen, “Stress, heat shock proteins, and autoimmunity: how immune responses to heat shock proteins are to be used for the control of chronic inflammatory diseases,” Annals of the New York Academy of Sciences, vol. 1113, pp. 217–237, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. F. J. Quintana, P. Carmi, F. Mor, and I. R. Cohen, “Inhibition of adjuvant-induced arthritis by DNA vaccination with the 70-kd or the 90-kd human heat-shock protein: immune cross-regulation with the 60-kd heat-shock protein,” Arthritis and Rheumatism, vol. 50, no. 11, pp. 3712–3720, 2004. View at Publisher · View at Google Scholar · View at Scopus
  27. T. J. Borges, L. Wieten, M. J. van Herwijnen et al., “The anti-inflammatory mechanisms of Hsp70,” Frontiers in Immunology, vol. 3, p. 95, 2012. View at Google Scholar
  28. S. K. Calderwood, M. A. Khaleque, D. B. Sawyer, and D. R. Ciocca, “Heat shock proteins in cancer: chaperones of tumorigenesis,” Trends in Biochemical Sciences, vol. 31, no. 3, pp. 164–172, 2006. View at Publisher · View at Google Scholar · View at Scopus
  29. D. R. Ciocca and S. K. Calderwood, “Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications,” Cell Stress and Chaperones, vol. 10, no. 2, pp. 86–103, 2005. View at Publisher · View at Google Scholar · View at Scopus
  30. J. Trepel, M. Mollapour, G. Giaccone, and L. Neckers, “Targeting the dynamic HSP90 complex in cancer,” Nature Reviews Cancer, vol. 10, no. 8, pp. 537–549, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. S. K. Calderwood and J. Gong, “Molecular chaperones in mammary cancer growth and breast tumor therapy,” ournal of Cellular Biochemistry, vol. 113, no. 4, pp. 1096–1103, 2011. View at Google Scholar
  32. P. Srivastava, “Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses,” Annual Review of Immunology, vol. 20, pp. 395–425, 2002. View at Publisher · View at Google Scholar · View at Scopus
  33. A. G. Pockley, “Heat shock proteins, inflammation, and cardiovascular disease,” Circulation, vol. 105, no. 8, pp. 1012–1017, 2002. View at Publisher · View at Google Scholar · View at Scopus
  34. S. S. Mambula and S. K. Calderwood, “Heat shock protein 70 is secreted from tumor cells by a nonclassical pathway involving lysosomal endosomes,” Journal of Immunology, vol. 177, no. 11, pp. 7849–7857, 2006. View at Google Scholar · View at Scopus
  35. S. S. Mambula and S. K. Calderwood, “Heat induced release of Hsp70 from prostate carcinoma cells involves both active secretion and passive release from necrotic cells,” International Journal of Hyperthermia, vol. 22, no. 7, pp. 575–585, 2006. View at Publisher · View at Google Scholar · View at Scopus
  36. F. Chalmin, S. Ladoire, G. Mignot et al., “Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells,” Journal of Clinical Investigation, vol. 120, no. 2, pp. 457–471, 2010. View at Publisher · View at Google Scholar · View at Scopus
  37. P. Stocki, X. N. Wang, and A. M. Dickinson, “Inducible heat shock protein 70 reduces T cell responses and stimulatory capacity of monocyte-derived dendritic cells,” The Journal of Biological Chemistry, no. 287, pp. 12387–12394, 2012. View at Google Scholar
  38. S. Banerjee, C. F. L. Lin, K. A. Skinner et al., “Heat shock protein 27 differentiates tolerogenic macrophages that may support human breast cancer progression,” Cancer Research, vol. 71, no. 2, pp. 318–327, 2011. View at Publisher · View at Google Scholar · View at Scopus
  39. C. L. Miller-Graziano, A. De, K. Laudanski, T. Herrmann, and S. Bandyopadhyay, “HSP27: an anti-inflammatory and immunomodulatory stress protein acting to dampen immune function,” Novartis Foundation Symposium, vol. 291, pp. 196–208, 2008. View at Google Scholar · View at Scopus
  40. R. M. Vabulas, P. Ahmad-Nejad, C. da Costa et al., “Endocytosed HSP60s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin-1 receptor signaling pathway in innate immune cells,” Journal of Biological Chemistry, vol. 276, no. 33, pp. 31332–31339, 2001. View at Publisher · View at Google Scholar · View at Scopus
  41. J. A. Aalberse, B. Kapitein, S. de Roock et al., “Cord blood CD4+ T cells respond to self heat shock protein 60 (HSP60),” PLoS ONE, vol. 6, Article ID e24119, 2011. View at Google Scholar
  42. I. De Kleer, Y. Vercoulen, M. Klein et al., “CD30 discriminates heat shock protein 60-induced FOXP3+ CD4+ T cells with a regulatory phenotype,” Journal of Immunology, vol. 185, no. 4, pp. 2071–2079, 2010. View at Publisher · View at Google Scholar · View at Scopus
  43. J. H. Ma, Y. F. Sui, J. Ye et al., “Heat shock protein 70/MAGE-3 fusion protein vaccine can enhance cellular and humoral immune responses to MAGE-3 in vivo,” Cancer Immunology, Immunotherapy, vol. 54, no. 9, pp. 907–914, 2005. View at Publisher · View at Google Scholar · View at Scopus
  44. S. Murata, Y. Minami, M. Minami, T. Chiba, and K. Tanaka, “CHIP is a chaperone-dependent E3 ligase that ubiquitylates unfolded protein,” EMBO Reports, vol. 2, no. 12, pp. 1133–1138, 2001. View at Publisher · View at Google Scholar · View at Scopus
  45. M. Cohen-Sfady, M. Pevsner-Fischer, R. Margalit, and I. R. Cohen, “Heat shock protein 60, via MyD88 innate signaling, protects B cells from apoptosis, spontaneous and induced,” Journal of Immunology, vol. 183, no. 2, pp. 890–896, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. M. Cohen-Sfady, G. Nussbaum, M. Pevsner-Fischer et al., “Heat shock protein 60 activates B cells via the TLR4-MyD88 pathway,” Journal of Immunology, vol. 175, no. 6, pp. 3594–3602, 2005. View at Google Scholar · View at Scopus
  47. N. Štrbo, K. Yamazaki, K. Lee, D. Rukavina, and E. R. Podack, “Heat shock fusion protein gp96-Ig mediates strong CD8 CTL expansion in vivo,” American Journal of Reproductive Immunology, vol. 48, no. 4, pp. 220–225, 2002. View at Publisher · View at Google Scholar · View at Scopus
  48. K. Yamazaki, T. Nguyen, and E. R. Podack, “Cutting edge: tumor secreted heat shock-fusion protein elicits CD8 cells for rejection,” Journal of Immunology, vol. 163, no. 10, pp. 5178–5182, 1999. View at Google Scholar · View at Scopus
  49. S. H. Beachy, A. J. Kisailus, E. A. Repasky, J. R. Subjeck, X. Y. Wang, and A. L. Kazim, “Engineering secretable forms of chaperones for immune modulation and vaccine development,” Methods, vol. 43, no. 3, pp. 184–193, 2007. View at Publisher · View at Google Scholar · View at Scopus
  50. P. Gao, X. Sun, X. Chen, J. Subjeck, and X. Y. Wang, “Secretion of stress protein grp170 promotes immune-mediated inhibition of murine prostate tumor,” Cancer Immunology, Immunotherapy, vol. 58, no. 8, pp. 1319–1328, 2009. View at Publisher · View at Google Scholar · View at Scopus
  51. A. Murshid, J. Gong, M. A. Stevenson, and S. KCalderwood, “Heat shock proteins and cancer vaccines: developments in the past decade and chaperoning in the decade to come,” Expert Review of Vaccines, vol. 10, pp. 1553–1568, 2011. View at Google Scholar
  52. H. Udono and P. K. Srivastava, “Heat shock protein 70-associated peptides elicit specific cancer immunity,” Journal of Experimental Medicine, vol. 178, no. 4, pp. 1391–1396, 1993. View at Google Scholar · View at Scopus
  53. A. Melcher, S. Todryk, N. Hardwick, M. Ford, M. Jacobson, and R. G. Vile, “Tumor immunogenicity is determined by the mechanism of cell death via induction of heat shock protein expression,” Nature Medicine, vol. 4, no. 5, pp. 581–587, 1998. View at Publisher · View at Google Scholar · View at Scopus
  54. X. Y. Wang, L. Kazim, E. A. Repasky, and J. R. Subjeck, “Characterization of heat shock protein 110 and glucose-regulated protein 170 as cancer vaccines and the effect of fever-range hyperthermia on vaccine activity,” Journal of Immunology, vol. 166, no. 1, pp. 490–497, 2001. View at Google Scholar · View at Scopus
  55. E. Noessner, R. Gastpar, V. Milani et al., “Tumor-derived heat shock protein 70 peptide complexes are cross-presented by human dendritic cells,” Journal of Immunology, vol. 169, no. 10, pp. 5424–5432, 2002. View at Google Scholar · View at Scopus
  56. M. H. Manjili, X. Y. Wang, X. Chen et al., “HSP110-HER2/neu chaperone complex vaccine induces protective immunity against spontaneous mammary tumors in HER-2/neu transgenic mice,” Journal of Immunology, vol. 171, no. 8, pp. 4054–4061, 2003. View at Google Scholar · View at Scopus
  57. V. Mazzaferro, J. Coppa, M. G. Carrabba et al., “Vaccination with autologous tumor-derived heat-shock protein Gp96 after liver resection for metastatic colorectal cancer,” Clinical Cancer Research, vol. 9, no. 9, pp. 3235–3245, 2003. View at Google Scholar · View at Scopus
  58. M. P. Mayer, D. Brehmer, C. S. Gässler, and B. Bukau, “Hsp70 chaperone machines,” Advances in Protein Chemistry, vol. 59, pp. 1–44, 2001. View at Publisher · View at Google Scholar · View at Scopus
  59. A. Murshid, J. Gong, and S. K. Calderwood, “Purification, preparation and use of a chaperone-peptide complexes for tumor immunotherapy,” Methods in Molecular Biology. In press.
  60. R. Y. Chandawarkar, M. S. Wagh, and P. K. Srivastava, “The dual nature of specific immunological activity of tumor-derived gp96 preparations,” Journal of Experimental Medicine, vol. 189, no. 9, pp. 1437–1442, 1999. View at Publisher · View at Google Scholar · View at Scopus
  61. W. Van Eden, R. Van Der Zee, and B. Prakken, “Heat-shock proteins induce T-cell regulation of chronic inflammation,” Nature Reviews Immunology, vol. 5, no. 4, pp. 318–330, 2005. View at Publisher · View at Google Scholar · View at Scopus
  62. Y. Delneste, G. Magistrelli, J. F. Gauchat et al., “Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation,” Immunity, vol. 17, no. 3, pp. 353–362, 2002. View at Publisher · View at Google Scholar · View at Scopus
  63. H. Singh-Jasuja, R. E. M. Toes, P. Spee et al., “Cross-presentation of glycoprotein 96-associated antigens: on major histocompatibility complex class I molecules requires receptor-mediated endocytosis,” Journal of Experimental Medicine, vol. 191, no. 11, pp. 1965–1974, 2000. View at Publisher · View at Google Scholar · View at Scopus
  64. A. Murshid, J. Gong, and S. K. Calderwood, “Heat shock protein 90 mediates efficient antigen cross presentation through the scavenger receptor expressed by endothelial cells-I,” Journal of Immunology, vol. 185, no. 5, pp. 2903–2917, 2010. View at Publisher · View at Google Scholar · View at Scopus
  65. C. V. Nicchitta, D. M. Carrick, and J. C. Baker-LePain, “The messenger and the message: gp96 (GRP94)-peptide interactions in cellular immunity,” Cell Stress and Chaperones, vol. 9, no. 4, pp. 325–331, 2004. View at Publisher · View at Google Scholar · View at Scopus
  66. A. R. Jockheck-Clark, E. V. Bowers, M. B. Totonchy, J. Neubauer, S. V. Pizzo, and C. V. Nicchitta, “Re-examination of CD91 function in GRP94 (glycoprotein 96) surface binding, uptake, and peptide cross-presentation,” Journal of Immunology, vol. 185, no. 11, pp. 6819–6830, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. J. R. Thériault, H. Adachi, and S. K. Calderwood, “Role of scavenger receptors in the binding and internalization of heat shock protein 70,” Journal of Immunology, vol. 177, no. 12, pp. 8604–8611, 2006. View at Google Scholar · View at Scopus
  68. R. J. Binder, D. K. Han, and P. K. Srivastava, “CD91: a receptor for heat shock protein gp96,” Nature Immunology, vol. 1, no. 2, pp. 151–155, 2000. View at Google Scholar · View at Scopus
  69. A. Murshid, J. Gong, and S. K. Calderwood, “The role of heat shock proteins in antigen cross presentation,” Frontiers in Immunology, vol. 3, article 63, 2012. View at Google Scholar
  70. J. R. Thériault, S. S. Mambula, T. Sawamura, M. A. Stevenson, and S. K. Calderwood, “Extracellular HSP70 binding to surface receptors present on antigen presenting cells and endothelial/epithelial cells,” FEBS Letters, vol. 579, no. 9, pp. 1951–1960, 2005. View at Publisher · View at Google Scholar · View at Scopus
  71. J. Gong, B. Zhu, A. Murshid et al., “T cell activation by heat shock protein 70 vaccine requires TLR signaling and scavenger receptor expressed by endothelial cells-1,” Journal of Immunology, vol. 183, no. 5, pp. 3092–3098, 2009. View at Publisher · View at Google Scholar · View at Scopus
  72. T. Imai, Y. Kato, C. Kajiwara et al., “Heat shock protein 90 (HSP90) contributes to cytosolic translocation of extracellular antigen for crosspresentation by dendritic cells,” The Proceedings of the National Academy of Sciences of the United States of America, vol. 108, pp. 16363–16368, 2011. View at Google Scholar
  73. J. Oura, Y. Tamura, K. Kamiguchi et al., “Extracellular heat shock protein 90 plays a role in translocating chaperoned antigen from endosome to proteasome for generating antigenic peptide to be cross-presented by dendritic cells,” International Immunology, vol. 23, no. 4, pp. 223–237, 2011. View at Publisher · View at Google Scholar · View at Scopus
  74. A. Lev, P. Dimberu, S. R. Das et al., “Efficient cross-priming of antiviral CD8+ T cells by antigen donor cells is GRP94 independent,” Journal of Immunology, vol. 183, no. 7, pp. 4205–4210, 2009. View at Publisher · View at Google Scholar · View at Scopus
  75. C. Kurts, B. W. S. Robinson, and P. A. Knolle, “Cross-priming in health and disease,” Nature Reviews Immunology, vol. 10, no. 6, pp. 403–414, 2010. View at Publisher · View at Google Scholar · View at Scopus
  76. S. R. M. Bennett, F. R. Carbone, F. Karamalis, R. A. Flavell, J. F. A. P. Miller, and W. R. Heath, “Help for cytotoxic-T-cell responses is mediated by CD4O signalling,” Nature, vol. 393, no. 6684, pp. 478–480, 1998. View at Google Scholar · View at Scopus
  77. M. Croft, “Co-stimulatory members of the TNFR family: keys to effective T-cell immunity?” Nature Reviews Immunology, vol. 3, no. 8, pp. 609–620, 2003. View at Google Scholar · View at Scopus
  78. P. Matzinger, “The danger model: a renewed sense of self,” Science, vol. 296, no. 5566, pp. 301–305, 2002. View at Publisher · View at Google Scholar · View at Scopus
  79. M. S. Hayden and S. Ghosh, “Signaling to NF-κB,” Genes and Development, vol. 18, no. 18, pp. 2195–2224, 2004. View at Publisher · View at Google Scholar · View at Scopus
  80. A. Tesniere, L. Apetoh, F. Ghiringhelli et al., “Immunogenic cancer cell death: a key-lock paradigm,” Current Opinion in Immunology, vol. 20, no. 5, pp. 504–511, 2008. View at Publisher · View at Google Scholar · View at Scopus
  81. K. L. Rock, A. Hearn, C. J. Chen, and Y. Shi, “Natural endogenous adjuvants,” Springer Seminars in Immunopathology, vol. 26, no. 3, pp. 231–246, 2005. View at Publisher · View at Google Scholar · View at Scopus
  82. S. K. Calderwood, A. Murshid, and J. Gong, “Heat shock proteins: conditional mediators of inflammation in tumor immunity,” Frontiers in Immunology, vol. 3, article 75, 2012. View at Google Scholar
  83. K. Takeda, T. Kaisho, and S. Akira, “Toll-like receptors,” Annual Review of Immunology, vol. 21, pp. 335–376, 2003. View at Publisher · View at Google Scholar · View at Scopus
  84. A. Asea, S. K. Kraeft, E. A. Kurt-Jones et al., “HSP70 stimulates cytokine production through a CD 14-dependant pathway, demonstrating its dual role as a chaperone and cytokine,” Nature Medicine, vol. 6, no. 4, pp. 435–442, 2000. View at Publisher · View at Google Scholar · View at Scopus
  85. B. Gao and M. F. Tsan, “Induction of cytokines by heat shock proteins and endotoxin in murine macrophages,” Biochemical and Biophysical Research Communications, vol. 317, no. 4, pp. 1149–1154, 2004. View at Publisher · View at Google Scholar · View at Scopus
  86. S. K. Calderwood, J. Gong, and A. Murshid, “Heat shock proteins: conditional mediators of inflammation in tumor immunity,” Frontiers in Inflammation, vol. 3, article 75, 2012. View at Publisher · View at Google Scholar
  87. Y. Enomoto, A. Bharti, A. A. Khaleque et al., “Enhanced immunogenicity of heat shock protein 70 peptide complexes from dendritic cell-tumor fusion cells,” Journal of Immunology, vol. 177, no. 9, pp. 5946–5955, 2006. View at Google Scholar · View at Scopus
  88. G. Multhoff and L. E. Hightower, “Distinguishing integral and receptor-bound heat shock protein 70 (Hsp70) on the cell surface by Hsp70-specific antibodies,” Cell Stress and Chaperones, vol. 16, no. 3, pp. 251–255, 2011. View at Publisher · View at Google Scholar · View at Scopus
  89. C. Gross, W. Koelch, A. DeMaio, N. Arispe, and G. Multhoff, “Cell surface-bound heat shock protein 70 (Hsp70) mediates perforin-independent apoptosis by specific binding and uptake of granzyme B,” Journal of Biological Chemistry, vol. 278, no. 42, pp. 41173–41181, 2003. View at Publisher · View at Google Scholar · View at Scopus
  90. L. Wang, L. Rollins, Q. Gu, S. Y. Chen, and X. F. Huang, “A Mage3/Heat Shock Protein70 DNA vaccine induces both innate and adaptive immune responses for the antitumor activity,” Vaccine, vol. 28, no. 2, pp. 561–570, 2009. View at Publisher · View at Google Scholar · View at Scopus
  91. J. Gong, Y. Zhang, J. Durfee et al., “A heat shock protein 70-based vaccine with enhanced immunogenicity for clinical use,” Journal of Immunology, vol. 184, no. 1, pp. 488–496, 2010. View at Publisher · View at Google Scholar · View at Scopus
  92. D. Weng, S. K. Calderwood, and J. Gong, “Preparation of a heat shock proteinbased vaccine from dendritic cells,” Methods in Molecular Biology, vol. 787, pp. 255–65, 2011. View at Google Scholar
  93. G. A. Daniels, L. Sanchez-Perez, R. M. Diaz et al., “A simple method to cure established tumors by inflammatory killing of normal cells,” Nature Biotechnology, vol. 22, no. 9, pp. 1125–1132, 2004. View at Publisher · View at Google Scholar · View at Scopus
  94. T. Kottke, L. Sanchez-Perez, R. M. Diaz et al., “Induction of hsp70-mediated Th17 autoimmunity can be exploited as immunotherapy for metastatic prostate cancer,” Cancer Research, vol. 67, no. 24, pp. 11970–11979, 2007. View at Publisher · View at Google Scholar · View at Scopus
  95. B. Afzali, G. Lombardi, R. I. Lechler, and G. M. Lord, “The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease,” Clinical and Experimental Immunology, vol. 148, no. 1, pp. 32–46, 2007. View at Publisher · View at Google Scholar · View at Scopus
  96. E. L. Spaeth, J. L. Dembinski, A. K. Sasser et al., “Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression,” PLoS ONE, vol. 4, no. 4, Article ID e4992, 2009. View at Publisher · View at Google Scholar · View at Scopus
  97. T. Schatton, U. Schütte, N. Y. Frank et al., “Modulation of T-cell activation by malignant melanoma initiating cells,” Cancer Research, vol. 70, no. 2, pp. 697–708, 2010. View at Publisher · View at Google Scholar · View at Scopus
  98. P. K. Srivastava, “Therapeutic cancer vaccines,” Current Opinion in Immunology, vol. 18, pp. 201–205, 2006. View at Google Scholar
  99. Y. Shi, J. E. Evans, and K. L. Rock, “Molecular identification of a danger signal that alerts the immune system to dying cells,” Nature, vol. 425, no. 6957, pp. 516–521, 2003. View at Publisher · View at Google Scholar · View at Scopus
  100. Q. Chen, D. T. Fisher, K. A. Clancy et al., “Fever-range thermal stress promotes lymphocyte trafficking across high endothelial venules via an interleukin 6 trans-signaling mechanism,” Nature Immunology, vol. 7, no. 12, pp. 1299–1308, 2006. View at Publisher · View at Google Scholar · View at Scopus
  101. S. Demaria, N. Bhardwaj, W. H. McBride, and S. C. Formenti, “Combining radiotherapy and immunotherapy: a revived partnership,” International Journal of Radiation Oncology Biology Physics, vol. 63, no. 3, pp. 655–666, 2005. View at Publisher · View at Google Scholar · View at Scopus
  102. A. Zerbini, M. Pilli, F. Fagnoni et al., “Increased immunostimulatory activity conferred to antigen-presenting cells by exposure to antigen extract from hepatocellular carcinoma after radiofrequency thermal ablation,” Journal of Immunotherapy, vol. 31, no. 3, pp. 271–282, 2008. View at Publisher · View at Google Scholar · View at Scopus
  103. J. Dulos, G. J. Carven, S. J. van Boxtel et al., “PD-1 blockade augments Th1 and Th17 and suppresses Th2 responses in peripheral blood from patients with prostate and advanced melanoma cancer,” Journal of Immunotherapy, vol. 35, pp. 169–178, 2012. View at Google Scholar
  104. A. A. Tarhini and J. M. Kirkwood, “CTLA-4-blocking immunotherapy with ipilimumab for advanced melanoma,” Oncology, vol. 24, no. 14, pp. 1302–1304, 2010. View at Google Scholar · View at Scopus
  105. L. Chen, “Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity,” Nature Reviews Immunology, vol. 4, no. 5, pp. 336–347, 2004. View at Google Scholar · View at Scopus
  106. A. Sah, M. Bhattacharya-Chatterjee, K. A. Foon, E. Celis, and S. K. Chatterjee, “Stimulatory effects of CpG ollgodeoxynucleotide on dendritic cell-based immunotherapy of colon cancer in CEA/HLA-A2 transgenic mice,” International Journal of Cancer, vol. 124, no. 4, pp. 877–888, 2009. View at Publisher · View at Google Scholar · View at Scopus