Hyperthermia on immune regulation: a temperature's story.

Over the last decade the linkage between hyperthermia, heat shock proteins and fever with the body's immune system has been well investigated. The immunomodulatory function of hyperthermia has been found to be quite sensitively regulated by temperature, as different levels of heating can bring different modulatory effect on different sensitive targets. Understanding these intrinsic mechanisms could bring new inspirations on the design of clinical trials combining local tumor hyperthermia with immunotherapy in cancer patients. This review will attempt to tell the story about the effect of temperature on immune regulation, with special emphasis on the clinical application of hyperthermia and the feasibility of combining it with immunotherapy in the clinic.

[1]  E. Conway de Macario,et al.  Sick chaperones, cellular stress, and disease. , 2005, The New England journal of medicine.

[2]  M. Caligiuri,et al.  Tumor cell apoptosis, lymphocyte recruitment and tumor vascular changes are induced by low temperature, long duration (fever‐like) whole body hyperthermia , 1998, Journal of cellular physiology.

[3]  J. Papadimitriou,et al.  The effect of mild hyperthermia on the morphology and function of murine resident peritoneal macrophages. , 1991, Experimental and molecular pathology.

[4]  M. Suckow,et al.  Prevention of human PC-346C prostate cancer growth in mice by a xenogeneic tissue vaccine , 2007, Cancer Immunology, Immunotherapy.

[5]  K. Hirata,et al.  Efficient Cross-Presentation by Heat Shock Protein 90-Peptide Complex-Loaded Dendritic Cells via an Endosomal Pathway , 2007, The Journal of Immunology.

[6]  E. Repasky,et al.  Regulation of immune activity by mild (fever-range) whole body hyperthermia: effects on epidermal Langerhans cells , 2000, Cell stress & chaperones.

[7]  H. Kolb,et al.  Cutting Edge: Heat Shock Protein 60 Is a Putative Endogenous Ligand of the Toll-Like Receptor-4 Complex1 , 2000, The Journal of Immunology.

[8]  P. Srivastava,et al.  Heat shock protein vaccines against cancer. , 1993, Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy.

[9]  B. Vikram,et al.  Flt3-ligand administration after radiation therapy prolongs survival in a murine model of metastatic lung cancer. , 1999, Cancer research.

[10]  P. Srivastava,et al.  Heat Shock Up-Regulates lmp2 and lmp7 and Enhances Presentation of Immunoproteasome-Dependent Epitopes1 , 2006, The Journal of Immunology.

[11]  E. Repasky,et al.  Heat shock proteins as vaccine adjuvants in infections and cancer. , 2006, Drug discovery today.

[12]  Tinghua Cao,et al.  Hyperthermia Enhances CTL Cross-Priming1 , 2006, The Journal of Immunology.

[13]  B. St. Croix,et al.  Tumor endothelial markers: new targets for cancer therapy , 2004, Current opinion in oncology.

[14]  R. Kaufman,et al.  The mammalian unfolded protein response. , 2003, Annual review of biochemistry.

[15]  S. Nahum Goldberg,et al.  Radiofrequency tumor ablation: principles and techniques , 2001 .

[16]  F. Hartl,et al.  CD40, an extracellular receptor for binding and uptake of Hsp70–peptide complexes , 2002, The Journal of cell biology.

[17]  P RITOSSA.  [Problems of prophylactic vaccinations of infants]. , 1962, Rivista dell'Istituto sieroterapico italiano.

[18]  A. Hoos,et al.  Vaccination with heat shock protein–peptide complexes: from basic science to clinical applications , 2003, Expert review of vaccines.

[19]  U. Hobohm.  Fever therapy revisited , 2005, British Journal of Cancer.

[20]  K. Ahrar,et al.  Spontaneous regression of pulmonary metastases from renal cell carcinoma after radio frequency ablation of primary tumor: an in situ tumor vaccine? , 2003, The Journal of urology.

[21]  Carl G. Figdor,et al.  In Situ Tumor Ablation Creates an Antigen Source for the Generation of Antitumor Immunity , 2004, Cancer Research.

[22]  R. Young,et al.  A proposed mechanism for the induction of cytotoxic T lymphocyte production by heat shock fusion proteins. , 2000, Immunity.

[23]  P. Srivastava,et al.  Combination of Imatinib Mesylate with Autologous Leukocyte-Derived Heat Shock Protein and Chronic Myelogenous Leukemia , 2005, Clinical Cancer Research.

[24]  P. Srivastava,et al.  A phase II trial of vaccination with autologous, tumor-derived heat-shock protein peptide complexes Gp96, in combination with GM-CSF and interferon-α in metastatic melanoma patients , 2006, Cancer Immunology, Immunotherapy.

[25]  Duff Gw.  Is fever beneficial to the host: a clinical perspective. , 1986, The Yale journal of biology and medicine.

[26]  Xuetao Cao,et al.  Fever range temperature promotes TLR4 expression and signaling in dendritic cells. , 2007, Life sciences.

[27]  M. Manjili,et al.  Cancer immunotherapy: stress proteins and hyperthermia , 2002, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[28]  S. Pizzo,et al.  Scavenger receptor‐A mediates gp96/GRP94 and calreticulin internalization by antigen‐presenting cells , 2003, The EMBO journal.

[29]  V. Ostapenko,et al.  Increased liver temperature efficiently augments human cellular immune response: T-cell activation and possible monocyte translocation , 2006, Cancer Immunology, Immunotherapy.

[30]  J. Eriksson,et al.  Fever-Like Hyperthermia Controls T Lymphocyte Persistence by Inducing Degradation of Cellular FLIPshort1 , 2007, The Journal of Immunology.

[31]  P. Matzinger.  Tolerance, danger, and the extended family. , 1994, Annual review of immunology.

[32]  Yufei Wang,et al.  Heat shock proteins generate β‐chemokines which function as innate adjuvants enhancing adaptive immunity , 2000 .

[33]  H. Rammensee,et al.  The heat shock protein gp96 induces maturation of dendritic cells and down‐regulation of its receptor , 2000, European journal of immunology.

[34]  Laurence Zitvogel,et al.  Toll-like receptor 4–dependent contribution of the immune system to anticancer chemotherapy and radiotherapy , 2007, Nature Medicine.

[35]  N. J. Roberts.  Temperature and host defense. , 1979, Microbiological reviews.

[36]  Carsten J. Kirschning,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* , 2001, The Journal of Biological Chemistry.

[37]  L. Frati,et al.  Hyperthermia Enhances CD95-Ligand Gene Expression in T Lymphocytes1 , 2005, The Journal of Immunology.

[38]  E. Repasky,et al.  Emerging evidence indicates that physiologically relevant thermal stress regulates dendritic cell function , 2006, Cancer Immunology, Immunotherapy.

[39]  G. Missale,et al.  Radiofrequency thermal ablation of hepatocellular carcinoma liver nodules can activate and enhance tumor-specific T-cell responses. , 2006, Cancer research.

[40]  T. Tobe,et al.  Effect of heat treatment on tumor cells and antitumor effector cells. , 1990, Cancer research.

[41]  C. Garrido,et al.  Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy , 2007, Journal of leukocyte biology.

[42]  J. Le Pendu,et al.  Co-segregation of tumor immunogenicity with expression of inducible but not constitutive hsp70 in rat colon carcinomas. , 1995, Journal of immunology.

[43]  D. Haemmerich,et al.  Thermal tumour ablation: Devices, clinical applications and future directions , 2005, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[44]  J. Zwischenberger,et al.  Whole-body hyperthermia: a review of theory, design and application , 2002, Perfusion.

[45]  S. Oizumi,et al.  Molecular and Cellular Requirements for Enhanced Antigen Cross-Presentation to CD8 Cytotoxic T Lymphocytes1 , 2007, The Journal of Immunology.

[46]  S. Kalnicki,et al.  Localized hyperthermia combined with intratumoral dendritic cells induces systemic antitumor immunity. , 2007, Cancer research.

[47]  Jun Zhu,et al.  Intratumoral injection of dendritic cells in combination with local hyperthermia induces systemic antitumor effect in patients with advanced melanoma , 2007, International journal of cancer.

[48]  Stuart K. Calderwood,et al.  HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine , 2000, Nature Medicine.

[49]  D. Fraker,et al.  Treatment of peritoneal carcinomatosis by continuous hyperthermic peritoneal perfusion with cisplatin. , 1996, Cancer treatment and research.

[50]  Haïtham Sghaier,et al.  Molecular chaperones: proposal of a systematic computer-oriented nomenclature and construction of a centralized database , 2004, Silico Biol..

[51]  C Caux,et al.  Immunobiology of dendritic cells. , 2000, Annual review of immunology.

[52]  C. Gross,et al.  Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. , 2005, Cancer research.

[53]  P. Srivastava,et al.  Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses. , 2002, Annual review of immunology.

[54]  Y. Delneste.  Scavenger receptors and heat-shock protein-mediated antigen cross-presentation. , 2004, Biochemical Society transactions.

[55]  Z. Prohászka.  Chaperones as part of immune networks. , 2007, Advances in experimental medicine and biology.

[56]  Gail ter Haar,et al.  High Intensity Focused Ultrasound: Past, present and future , 2007, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[57]  B. Ahring,et al.  Stress Genes and Proteins in the Archaea , 1999, Microbiology and Molecular Biology Reviews.

[58]  H. Kolb,et al.  Human 60-kDa heat-shock protein: a danger signal to the innate immune system. , 1999, Journal of immunology.

[59]  N. Bhardwaj,et al.  Primary Tumor Tissue Lysates Are Enriched in Heat Shock Proteins and Induce the Maturation of Human Dendritic Cells1 , 2001, The Journal of Immunology.

[60]  W. Cole.  Efforts to explain spontaneous regression of cancer , 1981, Journal of surgical oncology.

[61]  H. Honda,et al.  Intratumoral injection of immature dendritic cells enhances antitumor effect of hyperthermia using magnetic nanoparticles , 2005, International journal of cancer.

[62]  K. Yamazaki,et al.  Cutting edge: tumor secreted heat shock-fusion protein elicits CD8 cells for rejection. , 1999, Journal of immunology.

[63]  A. Wells,et al.  Heat shock proteins, tumor immunogenicity and antigen presentation: an integrated view. , 2000, Immunology today.

[64]  P. Srivastava,et al.  Heat Shock Proteins gp96 and hsp70 Activate the Release of Nitric Oxide by APCs1 , 2002, The Journal of Immunology.

[65]  Constantin Coussios,et al.  High intensity focused ultrasound: Physical principles and devices , 2007, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[66]  K. Fairchild,et al.  The role of fever in the infected host. , 2000, Microbes and infection.

[67]  R. Binder.  Heat Shock Protein Vaccines: From Bench to Bedside , 2006, International reviews of immunology.

[68]  Daniel T. Fisher,et al.  Fever-range thermal stress promotes lymphocyte trafficking across high endothelial venules via an interleukin 6 trans-signaling mechanism , 2006, Nature Immunology.

[69]  W. Hohenberger,et al.  [Regional hyperthermic perfusion--therapeutic concept and long term results]. , 1992, Langenbecks Archiv fur Chirurgie. Supplement. Kongressband. Deutsche Gesellschaft fur Chirurgie. Kongress.

[70]  A. Jouan,et al.  Fever‐like thermal conditions regulate the activation of maturing dendritic cells , 2003, Journal of leukocyte biology.

[71]  B. Raboy,et al.  Effect of heat shock on protein degradation in mammalian cells: involvement of the ubiquitin system. , 1987, The EMBO journal.

[72]  C. Vermeulen,et al.  Fever and the control of gram-negative bacteria. , 1994, Research in microbiology.

[73]  D. Jäger,et al.  Antigen‐specific immunotherapy and cancer vaccines , 2003, International journal of cancer.

[74]  M. Kluger.  The evolution and adaptive value of fever. , 1978, American scientist.

[75]  S. A. Cann,et al.  Dr William Coley and tumour regression: a place in history or in the future , 2003 .

[76]  P. Srivastava,et al.  Cutting Edge: Heat Shock Protein gp96 Induces Maturation and Migration of CD11c+ Cells In Vivo1 , 2000, The Journal of Immunology.

[77]  E. Atkins.  THE YALE JOURNAL OF BIOLOGY AND MEDICINE 55 (1982), 283-289 Fever: Its History, Cause, and Function , 1982 .

[78]  P. Galle,et al.  Stress protein/peptide complexes derived from autologous tumor tissue as tumor vaccines. , 1999, Biochemical pharmacology.

[79]  T. Wu,et al.  Enhancement of DNA vaccine potency by linkage of antigen gene to an HSP70 gene. , 2000, Cancer research.

[80]  P. Libby,et al.  Cutting Edge: Heat Shock Protein (HSP) 60 Activates the Innate Immune Response: CD14 Is an Essential Receptor for HSP60 Activation of Mononuclear Cells1 , 2000, The Journal of Immunology.

[81]  Pei Zhong,et al.  Investigation of HIFU-induced anti-tumor immunity in a murine tumor model , 2007, Journal of Translational Medicine.

[82]  H. Honda,et al.  Augmentation of MHC class I antigen presentation via heat shock protein expression by hyperthermia , 2001, Cancer Immunology, Immunotherapy.

[83]  C. Figdor,et al.  Synergy between in situ cryoablation and TLR9 stimulation results in a highly effective in vivo dendritic cell vaccine. , 2006, Cancer research.

[84]  K. Anderson,et al.  Phenotypic and Functional Effects of Heat Shock Protein 90 Inhibition on Dendritic Cell , 2007, The Journal of Immunology.

[85]  A. Menoret,et al.  The inducible Hsp70 as a marker of tumor immunogenicity , 2001, Cell stress & chaperones.

[86]  Michael Rehli,et al.  Novel Signal Transduction Pathway Utilized by Extracellular HSP70 , 2002, The Journal of Biological Chemistry.

[87]  K. Yamazaki,et al.  Heat Shock Fusion Protein gp96‐Ig Mediates Strong CD8 CTL Expansion in vivo , 2002, American journal of reproductive immunology.

[88]  Everson Tc,et al.  Spontaneous regression of cancer. , 1967, Progress in clinical cancer.

[89]  Laurence Zitvogel,et al.  Antigen presentation and T cell stimulation by dendritic cells. , 2002, Annual review of immunology.

[90]  K. Manova,et al.  Tumor endothelial marker 8 enhances tumor immunity in conjunction with immunization against differentiation Ag. , 2007, Cytotherapy.

[91]  P. Srivastava,et al.  Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway. , 2000, International immunology.

[92]  William W Mayo-Smith,et al.  Microwave ablation: principles and applications. , 2005, Radiographics : a review publication of the Radiological Society of North America, Inc.

[93]  D. Hanson,et al.  Fever, Temperature, and the Immune Response , 1997, Annals of the New York Academy of Sciences.

[94]  P. Csermely,et al.  Heat shock proteins as emerging therapeutic targets , 2005, British journal of pharmacology.

[95]  R. Kaufman,et al.  The unfolded protein response , 2006, Neurology.

[96]  E. Repasky,et al.  Enhancement of natural killer (NK) cell cytotoxicity by fever‐range thermal stress is dependent on NKG2D function and is associated with plasma membrane NKG2D clustering and increased expression of MICA on target cells , 2007, Journal of leukocyte biology.

[97]  Daniel T. Fisher,et al.  Dynamic control of lymphocyte trafficking by fever-range thermal stress , 2006, Cancer Immunology, Immunotherapy.

[98]  E. Repasky,et al.  Immunotherapy of cancer using heat shock proteins. , 2002, Frontiers in bioscience : a journal and virtual library.

[99]  T. Lindmo,et al.  Hyperthermia-induced shedding and masking of melanoma-associated antigen. , 1990, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[100]  E. Repasky,et al.  Thermal regulation of dendritic cell activation and migration from skin explants , 2003, International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group.

[101]  P. Srivastava,et al.  The heat-shock protein receptors: some answers and more questions. , 2004, Tissue antigens.

[102]  G. Gao,et al.  Effects of heat shock protein gp96 on human dendritic cell maturation and CTL expansion. , 2006, Biochemical and biophysical research communications.

[103]  D. Valmori,et al.  Cross‐presentation of NY‐ESO‐1 cytotoxic T lymphocyte epitope fused to human heat shock cognate protein 70 by dendritic cells , 2007, Cancer science.

[104]  Jonathan J. Lewis,et al.  Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: clinical and immunologic findings. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[105]  L. Lanier,et al.  A Signal Peptide Derived from hsp60 Binds HLA-E and Interferes with CD94/NKG2A Recognition , 2002, The Journal of experimental medicine.

[106]  P. Srivastava,et al.  CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. , 2001, Immunity.

[107]  Birger Mensel,et al.  Laser-induced thermotherapy. , 2006, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[108]  P. Srivastava,et al.  Heat‐Shock Proteins , 2003, Current protocols in immunology.

[109]  A. Skanes,et al.  Cryoablation: , 2004, Journal of cardiovascular electrophysiology.

[110]  Kayo Nakamura,et al.  Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation. , 2002, Immunity.

[111]  P. Srivastava,et al.  Fever-like temperature induces maturation of dendritic cells through induction of hsp90. , 2003, International immunology.

[112]  Carsten J. Kirschning,et al.  The Endoplasmic Reticulum-resident Heat Shock Protein Gp96 Activates Dendritic Cells via the Toll-like Receptor 2/4 Pathway* , 2002, The Journal of Biological Chemistry.

[113]  W. A. Soanes,et al.  Remission of metastatic lesions following cryosurgery in prostatic cancer: immunologic considerations. , 1970, The Journal of urology.

[114]  D. Hanson.  Fever and the immune response. The effects of physiological temperatures on primary murine splenic T-cell responses in vitro. , 1993, Journal of immunology.

[115]  B. Vikram,et al.  Flt3L Therapy following Localized Tumor Irradiation Generates Long-Term Protective Immune Response in Metastatic Lung Cancer: Its Implication in Designing a Vaccination Strategy , 2006, Oncology.

[116]  R. Paxton,et al.  The effects of hyperthermia on tumor carcinoembryonic antigen expression. , 1989, International journal of radiation oncology, biology, physics.

[117]  P. Matzinger,et al.  Danger signals: SOS to the immune system. , 2001, Current opinion in immunology.

[118]  K. Rock,et al.  The class II MHC-restricted presentation of endogenously synthesized ovalbumin displays clonal variation, requires endosomal/lysosomal processing, and is up-regulated by heat shock. , 1992, Journal of immunology.