RESUMO
Hydroxyl-methyl-glutaryl-Co-A reductase (HMGCR) immune mediated necrotising myopathy (IMNM) is a rare autoimmune myositis that is thought to be triggered by statins and responds to immunomodulation. We report a case of a woman in her 30s with HMGCR IMNM without a history of statin exposure who had a clear flare of her myositis after beginning mushroom supplements. Mushrooms are natural HMGCR inhibitors, and this is the first case to demonstrate a flare triggered by mushrooms in a patient with known HMGCR IMNM. This case highlights the importance of reviewing diet and supplements in patients with IMNM. It also emphasises the importance of strict statin avoidance for patients with IMNM even when the myositis is under good control.
Assuntos
Agaricales , Doenças Autoimunes , Suplementos Nutricionais , Doenças Musculares , Adulto , Autoanticorpos/imunologia , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Suplementos Nutricionais/efeitos adversos , Feminino , Humanos , Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hidroximetilglutaril-CoA Redutases/imunologia , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Músculo Esquelético/imunologia , Músculo Esquelético/patologia , Doenças Musculares/induzido quimicamente , Doenças Musculares/diagnóstico , Doenças Musculares/imunologia , Doenças Musculares/patologia , Miosite/induzido quimicamente , Miosite/diagnóstico , Miosite/imunologia , Miosite/patologia , Necrose/induzido quimicamente , Necrose/imunologia , Fitoterapia/efeitos adversos , Exacerbação dos SintomasRESUMO
The lack of effective pharmacological treatments for acute kidney injury (AKI) remains a significant public health problem. Given the involvement of apoptosis and regulated necrosis in the initiation and progression of AKI, the inhibition of cell death may contribute to AKI prevention/recovery. Curcuminoids are a family of plant polyphenols that exhibit attractive biological properties that make them potentially suitable for AKI treatment. Now, in cultured tubular cells, we demonstrated that a crosslinked self-assembled star-shaped polyglutamate (PGA) conjugate of bisdemethoxycurcumin (St-PGA-CL-BDMC) inhibits apoptosis and necroptosis induced by Tweak/TNFα/IFNγ alone or concomitant to caspase inhibition. St-PGA-CL-BDMC also reduced NF-κB activation and subsequent gene transcription. In vivo, St-PGA-CL-BDMC prevented renal cell loss and preserved renal function in mice with folic acid-induced AKI. Mechanistically, St-PGA-CL-BDMC inhibited AKI-induced apoptosis and expression of ferroptosis markers and also decreased the kidney expression of genes involved in tubular damage and inflammation, while preserving the kidney expression of the protective factor, Klotho. Thus, due to renal accumulation and attractive pharmacological properties, the application of PGA-based therapeutics may improve nephroprotective properties of current AKI treatments.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Diarileptanoides/farmacologia , Túbulos Renais/efeitos dos fármacos , Ácido Poliglutâmico/farmacologia , Substâncias Protetoras/farmacologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/imunologia , Injúria Renal Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Linhagem Celular , Diarileptanoides/química , Diarileptanoides/uso terapêutico , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Ácido Fólico/toxicidade , Glucuronidase/metabolismo , Humanos , Túbulos Renais/patologia , Proteínas Klotho , Camundongos , Conformação Molecular , NF-kappa B/metabolismo , Necrose/tratamento farmacológico , Necrose/imunologia , Necrose/patologia , Ácido Poliglutâmico/química , Ácido Poliglutâmico/uso terapêutico , Substâncias Protetoras/química , Substâncias Protetoras/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Relação Estrutura-Atividade , Transcrição Gênica/efeitos dos fármacosRESUMO
OBJECTIVES: In autoimmunity, autoantibodies (aAb) may be simple biomarkers of disease or true pathogenic effectors. A form of idiopathic inflammatory myopathy associated with anti-signal recognition particle (SRP) or anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) aAb has been individualised and is referred to as immune-mediated necrotising myopathy (IMNM). The level of aAb correlates with IMNM activity and disease may respond to immunosuppression, suggesting that they are pathogenic. We aimed to evaluate the pathogenicity of IgG from patients with anti-SRP or anti-HMGCR aAb in vivo by developing the first mouse model of IMNM. METHODS: IgG from patients suffering from anti-SRP or anti-HMGCR associated IMNM were passively transferred to wild-type, Rag2-/- or complement C3-/- mice. Muscle deficiency was evaluated by muscle strength on electrostimulation and grip test. Histological analyses were performed after haematoxylin/eosin staining or by immunofluorescence or immunohistochemistry analysis. Antibody levels were quantified by addressable laser bead assay (ALBIA). RESULTS: Passive transfer of IgG from patients suffering from IMNM to C57BL/6 or Rag2-/- mice provoked muscle deficiency. Pathogenicity of aAb was reduced in C3-/- mice while increased by supplementation with human complement. Breakage of tolerance by active immunisation with SRP or HMGCR provoked disease. CONCLUSION: This study demonstrates that patient-derived anti-SRP+ and anti-HMGCR+ IgG are pathogenic towards muscle in vivo through a complement-mediated mechanism, definitively establishing the autoimmune character of IMNM. These data support the use of plasma exchanges and argue for evaluating complement-targeting therapies in IMNM.
Assuntos
Autoanticorpos/imunologia , Hidroximetilglutaril-CoA Redutases/imunologia , Imunoglobulina G/imunologia , Miosite/imunologia , Partícula de Reconhecimento de Sinal/imunologia , Animais , Proteínas do Sistema Complemento/imunologia , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Força Muscular/imunologia , Músculo Esquelético/imunologia , Necrose/imunologiaRESUMO
The term acute tubular necrosis was thought to represent a misnomer derived from morphological studies of human necropsies and necrosis was thought to represent an unregulated passive form of cell death which was not amenable to therapeutic manipulation. Recent advances have improved our understanding of cell death in acute kidney injury. First, apoptosis results in cell loss, but does not trigger an inflammatory response. However, clumsy attempts at interfering with apoptosis (e.g. certain caspase inhibitors) may trigger necrosis and, thus, inflammation-mediated kidney injury. Second, and most revolutionary, the concept of regulated necrosis emerged. Several modalities of regulated necrosis were described, such as necroptosis, ferroptosis, pyroptosis and mitochondria permeability transition regulated necrosis. Similar to apoptosis, regulated necrosis is modulated by specific molecules that behave as therapeutic targets. Contrary to apoptosis, regulated necrosis may be extremely pro-inflammatory and, importantly for kidney transplantation, immunogenic. Furthermore, regulated necrosis may trigger synchronized necrosis, in which all cells within a given tubule die in a synchronized manner. We now review the different modalities of regulated necrosis, the evidence for a role in diverse forms of kidney injury and the new opportunities for therapeutic intervention.
Assuntos
Necrose Tubular Aguda/patologia , Terapia de Alvo Molecular/métodos , Necrose/fisiopatologia , Animais , Apoptose , Oxalato de Cálcio/toxicidade , Cisplatino/toxicidade , Citocinas/fisiologia , Avaliação Pré-Clínica de Medicamentos , Ácido Fólico/toxicidade , Humanos , Rim/irrigação sanguínea , Necrose Tubular Aguda/induzido quimicamente , Necrose Tubular Aguda/tratamento farmacológico , Camundongos , Camundongos Knockout , Proteínas de Transporte da Membrana Mitocondrial/fisiologia , Poro de Transição de Permeabilidade Mitocondrial , Modelos Biológicos , Necrose/classificação , Necrose/tratamento farmacológico , Necrose/imunologia , Traumatismo por Reperfusão/patologia , Terminologia como AssuntoRESUMO
Immunotherapeutic approaches to manage patients with advanced gastrointestinal malignancies are desired; however, mechanisms to incite tumor-specific immune responses remain to be elucidated. Rose bengal (RB) is toxic at low concentrations to malignant cells and may induce damage-associated molecular patterns; therefore, we investigated its potential as an immunomodulator in colon cancer. Murine and human colon cancer lines were treated with RB (10% in saline/PV-10) for cell cycle, cell death, and apoptosis assays. Damage-associated molecular patterns were assessed with western blot, ELISA, and flow cytometry. In an immunocompetent murine model of colon cancer, we demonstrate that tumors regress upon RB treatment, and that RB induces cell death in colon cancer cells through G2/M growth arrest and predominantly necrosis. RB-treated colon cancer cells expressed distinct hallmarks of immunogenic cell death (ICD), including enhanced expression of calreticulin and heat-shock protein 90 on the cell surface, a decrease in intracellular ATP, and the release of HMGB1. To confirm the ICD phenotype, we vaccinated immunocompetent animals with syngeneic colon cancer cells treated with RB. RB-treated tumors served as a vaccine against subsequent challenge with the same CT26 colon cancer tumor cells, and vaccination with in vitro RB-treated cells resulted in slower tumor growth following inoculation with colon cancer cells, but not with syngeneic non-CT26 cancer cells, suggesting a specific antitumor immune response. In conclusion, RB serves as an inducer of ICD that contributes to enhanced specific antitumor immunity in colorectal cancer.
Assuntos
Antineoplásicos/imunologia , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Morte Celular/imunologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/imunologia , Rosa Bengala/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Calreticulina/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Células HCT116 , Proteína HMGB1/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Células HT29 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Necrose/tratamento farmacológico , Necrose/imunologia , Necrose/metabolismoRESUMO
1. This study was to evaluate the effects of supplementary dietary selenium (Se) given as sodium selenite on host immune response against necrotic enteritis (NE) in commercial broiler chickens. 2. Chicks were fed from hatching on a non-supplemented diet or diets supplemented with different levels of Se (0.25, 0.50, and 1.00 Se mg/kg). To induce NE, broiler chickens were orally infected with Eimeria maxima at 14 d of age and then with Clostridium perfringens 4 d later using our previously established NE disease model. 3. NE-associated clinical signs and host protective immunity were determined by body weight changes, intestinal lesion scores, and serum antibodies against α-toxin and necrotic enteritis B (NetB) toxin. The effects of dietary Se on the gene expression of pro-inflammatory cytokines e.g., interleukin (IL)-1ß, IL-6, IL-8LITAF (lipopolysaccharide-induced TNFα-factor), tumour necrosis factor (TNF) SF15, and inducible nitric oxide synthase (iNOS), glutathione peroxidase 7 (GPx7), and avian ß-defensins (AvBD) 6, 8, and 13 (following NE infection) were analysed in the intestine and spleen. 4. The results showed that dietary supplementation of newly hatched broiler chicks with 0.25 Se mg/kg from hatch significantly reduced NE-induced gut lesions compared with infected birds given a non-supplemented diet. The levels of serum antibody against the NetB toxin in the chicks fed with 0.25 and 0.50 mg/kg Se were significantly higher than the non-supplemented control group. The transcripts for IL-1ß, IL-6, IL-8, iNOS, LITAF, and GPx7, as well as AvBD6, 8, and 13 were increased in the intestine and spleen of Se-supplemented groups, whereas transcript for TNFSF15 was decreased in the intestine. 5. It was concluded that dietary supplementation with optimum levels of Se exerted beneficial effects on host immune response to NE and reduced negative consequence of NE-induced immunopathology.
Assuntos
Galinhas , Suplementos Nutricionais , Imunidade Inata/fisiologia , Intestinos/imunologia , Necrose/veterinária , Doenças das Aves Domésticas/imunologia , Selenito de Sódio , Ração Animal/análise , Animais , Infecções por Clostridium/imunologia , Infecções por Clostridium/microbiologia , Infecções por Clostridium/parasitologia , Infecções por Clostridium/veterinária , Clostridium perfringens/fisiologia , Coccidiose/imunologia , Coccidiose/microbiologia , Coccidiose/parasitologia , Coccidiose/veterinária , Dieta/veterinária , Suplementos Nutricionais/análise , Suscetibilidade a Doenças/imunologia , Suscetibilidade a Doenças/microbiologia , Suscetibilidade a Doenças/parasitologia , Suscetibilidade a Doenças/veterinária , Eimeria/fisiologia , Enterite/imunologia , Enterite/microbiologia , Enterite/parasitologia , Enterite/veterinária , Intestinos/microbiologia , Intestinos/parasitologia , Masculino , Necrose/imunologia , Necrose/microbiologia , Necrose/parasitologia , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/parasitologia , Selenito de Sódio/administração & dosagem , Selenito de Sódio/metabolismo , Sódio na Dieta/administração & dosagemRESUMO
Major advances in dissecting mechanisms of NO-induced down-regulation of the anti-tumour specific T-cell function have been accomplished during the last decade. In this work, we studied the effects of a NO donor (AT38) on leukaemic Jurkat cell bioenergetics. Culturing Jurkat cells in the presence of AT38 triggered irreversible inhibition of cell respiration, led to the depletion of 50% of the intracellular ATP content and induced the arrest of cell proliferation and the loss of cell viability. Although a deterioration of the overall metabolic activity has been observed, glycolysis was stimulated, as revealed by the increase of glucose uptake and lactate accumulation rates as well as by the up-regulation of GLUT-1 and PFK-1 mRNA levels. In the presence of NO, cell ATP was rapidly consumed by energy-requiring apoptosis mechanisms; under a glucose concentration of about 12.7mM, cell death was switched from apoptosis into necrosis. Exposure of Jurkat cells to DMSO (1%, v/v), SA and AT55, the non-NO releasing moiety of AT38, failed to modulate neither cell proliferation nor bioenergetics. Thus, as for all NSAIDs, beneficial effects of AT38 on tumour regression are accompanied by the suppression of the immune system. We then showed that pre-treating Jurkat cells with low concentration of cyclosporine A, a blocker of the mitochondrial transition pore, attenuates AT38-induced inhibition of cell proliferation and suppresses cell death. Finally, we have studied and compared the effects of nitrite and nitrate on Jurkat cells to those of NO and we are providing evidence that nitrate, which is considered as a biologically inert anion, has a concentration and time-dependent immunosuppressive potential.
Assuntos
Metabolismo Energético/imunologia , Óxido Nítrico/imunologia , Trifosfato de Adenosina/imunologia , Trifosfato de Adenosina/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Proliferação de Células/efeitos dos fármacos , Respiração Celular/efeitos dos fármacos , Respiração Celular/imunologia , Relação Dose-Resposta a Droga , Metabolismo Energético/efeitos dos fármacos , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Glucose/imunologia , Glucose/metabolismo , Transportador de Glucose Tipo 1/genética , Glicólise/efeitos dos fármacos , Glicólise/imunologia , Humanos , Células Jurkat , Lactatos/imunologia , Lactatos/metabolismo , Leucemia de Células T/genética , Leucemia de Células T/imunologia , Leucemia de Células T/metabolismo , Necrose/imunologia , Nitratos/farmacologia , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/farmacologia , Fosfofrutoquinase-1/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Nitrito de Sódio/farmacologia , Fatores de TempoRESUMO
Clinical data of a single case of functional recovery and regeneration in pathologically altered foot tissue with extensive necrosis in during the course of therapy with the use of dietary supplement "Leiurus Arctica +" Clinical data indicates that the dietary supplement "Leiurus Arctica +" can be used as a wound healing agent.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Misturas Complexas/farmacologia , Dermatite Atópica/dietoterapia , Fármacos Dermatológicos/farmacologia , Suplementos Nutricionais , Necrose/dietoterapia , Cicatrização/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/isolamento & purificação , Misturas Complexas/isolamento & purificação , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Fármacos Dermatológicos/isolamento & purificação , Peixes/metabolismo , Pé/patologia , Pé/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Necrose/imunologia , Necrose/patologia , Recuperação de Função FisiológicaRESUMO
Colorectal cancer is the second leading cause of death in developed countries. Tumor therapies should on the one hand aim to stop the proliferation of tumor cells and to kill them, and on the other hand stimulate a specific immune response against residual cancer cells. Dying cells are modulators of the immune system contributing to anti-inflammatory or pro-inflammatory responses, depending on the respective cell death form. The positive therapeutic effects of temperature-controlled hyperthermia (HT), when combined with ionizing irradiation (X-ray), were the origin to examine whether combinations of X-ray with HT can induce immune activating tumor cell death forms, also characterized by the release of the danger signal HMGB1. Human colorectal tumor cells with differing radiosensitivities were treated with combinations of HT (41.5 degrees C for 1h) and X-ray (5 or 10Gy). Necrotic cell death was prominent after X-ray and could be further increased by HT. Apoptosis remained quite low in HCT 15 and SW480 cells. X-ray and combinations with HT arrested the tumor cells in the radiosensitive G2 cell cycle phase. The amount of released HMGB1 protein was significantly enhanced after combinatorial treatments in comparison to single ones. We conclude that combining X-ray with HT may induce anti-tumor immunity as a result of the predominant induction of inflammatory necrotic tumor cells and the release of HMGB1.
Assuntos
Neoplasias Colorretais/terapia , Proteína HMGB1/metabolismo , Hipertermia Induzida , Apoptose/imunologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/radioterapia , Terapia Combinada , Fase G2/efeitos da radiação , Humanos , Sistema Imunitário/efeitos da radiação , Necrose/imunologia , Tolerância a RadiaçãoRESUMO
Autoimmune diseases and cancer can be treated by influencing the immune system. Apo and nec cells are strong modulators of the immune system contributing to anti-inflammatory and pro-inflammatory responses, respectively. We examined which form of cell death was induced by HT and X-irradiation. Nec was the prominent form of cell death after combined treatment and the amount of dead cells was higher when exposing the cells to radiation before HT. Combined applications further led to an increased percentage of cells in a more radioresponsive G2 cell cycle phase. The danger signal HMGB1 is released when combining HT with radiation, a further hint that those treatments may induce inflammation and immune activation. We conclude that immune responses are appropriately adapted to the damage that has occurred and may contribute to anti-cancer immunity or chronic autoimmunity, respectively.
Assuntos
Apoptose/efeitos da radiação , Hipertermia Induzida/efeitos adversos , Inflamação/imunologia , Necrose/imunologia , Apoptose/imunologia , Linhagem Celular Tumoral , Proteína HMGB1/biossíntese , Proteína HMGB1/efeitos da radiação , Humanos , Raios XRESUMO
BACKGROUND: Prostate hyperthermia and photodynamic therapy can be delivered by a variety of procedures which result in a wide range of temperatures and light energy and cause different kinds of cell death. METHODS: We have addressed the immunogenic effect of heating and UVC irradiation on the prostate cancer (PCa) cell line LNCaP, by studying the release of Danger Associated Molecule Pattern (DAMP) molecules HSP70 and HMGB1 and the dendritic cell (DC) antigen-presenting efficiency. RESULTS: Intracellular upmodulation and extracellular release of HSP70 were inversely correlated. Mild temperatures (43-47 degrees C) induced an early increase of intracellular HSP70, whereas the highest temperature (56 degrees C) induced its extrusion from the cell. Likewise, UVC caused an immediate migration of HSP70 into the cell medium in the absence of any intracellular modulation. 56 degrees C and UVC also induced a robust release of HMGB1. The release of DAMP molecules was closely associated with post-apoptotic membrane damage, as shown by double Annexin V/propidium iodide staining, whereas beta-tubulin, a structural component of cell membranes, was specifically induced by 56 degrees C heating. Tumor uptake strongly impaired the cytokine-driven maturation of DCs and 56 degrees C heating led to a significant recovery of CD83 and CCR7 DC maturation markers, but did not influence the antigen cross-presentation activity. On the contrary, UVC-treated LNCaP had negligible effects on DC maturation, but increased the cross-priming of tumor specific CTL. CONCLUSIONS: These data may be of use in the design of effective non-surgical PCa ablations that combine tumor destruction with long lasting immunity.
Assuntos
Células Dendríticas/imunologia , Proteína HMGB1/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Hipertermia Induzida , Neoplasias da Próstata/imunologia , Raios Ultravioleta , Apresentação de Antígeno/imunologia , Apresentação de Antígeno/efeitos da radiação , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Células Dendríticas/metabolismo , Células Dendríticas/efeitos da radiação , Raios gama , Proteína HMGB1/isolamento & purificação , Humanos , Masculino , Necrose/imunologia , Necrose/metabolismo , Necrose/radioterapia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/terapia , Linfócitos T Citotóxicos/citologia , Linfócitos T Citotóxicos/imunologia , Tubulina (Proteína)/biossínteseRESUMO
Annexins are characterized by the ability to bind phospholipids of membranes in the presence of Ca2+. Annexin A5 represents a typical member of this protein family and is a natural occurring highly specific ligand for phosphatidylserine (PS). The exposure of PS is one major "eat me" signal for phagocytes of apoptotic and necrotic cells. Apoptotic cells are normally cleared via an anti-inflammatory pathway. In contrast, the uptake and removal of necrotic cells normally involves inflammation and an immune response. Interestingly, the lack of endogenous annexin A5 also leads to a reduced inflammatory potential of necrotic cells. Annexin A5 may interfere in vivo with the immunosuppressive effects of apoptotic cells since it preferentially binds PS with high affinity and inhibits apoptotic cell uptake by macrophages. In this review we focus on how defects in the clearance process can lead to chronic autoimmunity. Furthermore, the role of annexin A5 as important adjuvant for apoptotic cell-based tumour vaccines is discussed. The mechanism of how the immunogenicity of apoptotic cells can be restored by blocking their PS-dependent clearance is outlined in detail. Taken together, annexin A5 is an important modulator of the immune response against PS-exposing particles like apoptotic cells, necrotic cells, and certain viruses.
Assuntos
Anexina A5/fisiologia , Morte Celular/imunologia , Fagocitose/imunologia , Animais , Apoptose/imunologia , Humanos , Inflamação/fisiopatologia , Macrófagos/fisiologia , Necrose/imunologia , Neoplasias/imunologia , Neoplasias/patologia , Fosfatidilserinas/fisiologiaRESUMO
Heat shock proteins (HSPs) are highly conserved proteins whose syntheses are induced by a variety of stresses, including heat stress. Since the expression of HSPs, including HSP70, protects cells from heat-induced apoptosis, HSP expression has been considered to be a complicating factor in hyperthermia. On the other hand, recent reports have shown the importance of HSPs, such as HSP70, HSP90 and glucose-regulated protein 96 (gp96), in immune reactions. If HSP expression induced by hyperthermia is involved in tumor immunity, novel cancer immunotherapy based on this novel concept can be developed. In such a strategy, a tumor-specific hyperthermia system, which can heat the local tumor region to the intended temperature without damaging normal tissue, would be highly advantageous. To achieve tumor-specific hyperthermia, we have developed an intracellular hyperthermia system using magnetite nanoparticles. This novel hyperthermia system can induce necrotic cell death via HSP expression, which induces antitumor immunity. In the present article, cancer immunology and immunotherapy based on hyperthermia, and HSP expression are reviewed and discussed.