Functions of Heat Shock Proteins in Pathways of the Innate and Adaptive Immune System

Binder, Robert J.

doi:10.4049/jimmunol.1401417

Cited by 149 publications

(128 citation statements)

References 102 publications

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“…DFTD cells could be disrupted to increase immunogenicity, CpG or other TLR agonists would promote the response via innate immune cells, multiple immunizations followed by a boost. Frozen/thawed, or sonicated, cells could initially direct the immune response toward cytoplasmic antigens and potentially expose additional stimulatory molecules such as heat shock proteins [36]. High-dose ␥-irradiation is useful for inducing cell death for vaccination [37].…”

Section: Discussionmentioning

confidence: 99%

Evidence for induction of humoral and cytotoxic immune responses against devil facial tumor disease cells in Tasmanian devils (Sarcophilus harrisii) immunized with killed cell preparations

Kreiss

Brown

Tovar

et al. 2015

Vaccine

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Tasmanian devils (Sarcophilus harrisii) risk extinction from a contagious cancer, devil facial tumour disease (DFTD) in which the infectious agent is the tumor cell itself. Because devils are unable to produce an immune response against the tumor cells no devil has survived 'infection'. To promote an immune response we immunized healthy devils with killed DFTD tumor cells in the presence of adjuvants. Immune responses, including cytotoxicity and antibody production, were detected in five of the six devils. The incorporation of adjuvants that act via toll like receptors may provide additional signals to break 'immunological ignorance'. One of these devils was protected against a challenge with viable DFTD cells. This was a short-term protection as re-challenge one year later resulted in tumor growth. These results suggest that Tasmanian devils can generate immune responses against DFTD cells. With further optimization of immune stimulation it should be possible to protect Tasmanian devils against DFTD with an injectable vaccine.

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Section: Discussionmentioning

confidence: 99%

Evidence for induction of humoral and cytotoxic immune responses against devil facial tumor disease cells in Tasmanian devils (Sarcophilus harrisii) immunized with killed cell preparations

Kreiss

Brown

Tovar

et al. 2015

Vaccine

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“…We have not addressed directly whether Hsp70's role in this model lies mainly in antigen-chaperoning (33,38,39) or enhancing autophagy (40) or triggering DC maturation (41,42) with subsequent increase in T-cell stimulation. All of these known functions can be important and they likely play a synergistic role.…”

Section: Discussionmentioning

confidence: 99%

Cross-Presentation of the Oncofetal Tumor Antigen 5T4 from Irradiated Prostate Cancer Cells—A Key Role for Heat-Shock Protein 70 and Receptor CD91

Salimu

Spary

Al-Taei

et al. 2015

Cancer Immunology Research

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Immune responses contribute to the success of radiotherapy of solid tumors; however, the mechanism of triggering CD8 þ T-cell responses is poorly understood. Antigen cross-presentation from tumor cells by dendritic cells (DC) is a likely dominant mechanism to achieve CD8 þ T-cell stimulation. We established a cross-presentation model in which DCs present a naturally expressed oncofetal tumor antigen (5T4) from irradiated DU145 prostate cancer cells to 5T4-specific T cells. The aim was to establish which immunogenic signals are important in radiation-induced cross-presentation. Radiation (12 Gy) caused G 2 -M cell-cycle arrest and cell death, increased cellular 5T4 levels, high-mobility protein group-B1 (HMGB1) release, and surface calreticulin and heat-shock protein-70 (Hsp70) expression in DU145 cells. DCs phagocytosed irradiated tumor cells efficiently, followed by upregulation of CD86 on phagocytic DCs. CD8 þ 5T4-specific T cells, stimulated with these DCs, proliferated and produced IFNg. Inhibition of HMGB1 or the TRIF/MyD88 pathway only had a partial effect on T-cell stimulation. Unlike previous investigators, we found no evidence that DCs carrying Asp299Gly Toll-like receptor-4 (TLR4) single-nucleotide polymorphism had impaired ability to cross-present tumor antigen. However, pretreatment of tumor cells with Hsp70 inhibitors resulted in a highly statistically significant and robust prevention of antigen cross-presentation and CD86 upregulation on DCs cocultured with irradiated tumor cells. Blocking the Hsp70 receptor CD91 also abolished cross-presentation. Together, the results from our study demonstrate that irradiation induces immunologically relevant changes in tumor cells, which can trigger CD8 þ T-cell responses via a predominantly Hsp70-dependent antigen cross-presentation process. Cancer Immunol Res; 3(6); 678-88. Ó2015 AACR.

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“…Heat-shock proteins and major histocompatibility complex (MHC) molecules are the two systems involved in peptide antigen presentation. 19,21,22 Extracellular HSPs are able to interact directly with antigen-presenting cells (e.g., dendritic cells, macrophages) through the activation of various receptors (e.g., toll-like receptors 2 and 4; CD91) to produce danger signals, thus leading to innate immune responses. 19 Extracellular HSP27 has been shown to be anti-inflammatory, with responses depending on immune cell types.…”

Section: Regulation Of Immune Responses and Inflammationmentioning

confidence: 99%

Gut epithelial inducible heat-shock proteins and their modulation by diet and the microbiota

Arnal

Lallès

2016

Nutr Rev

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Functions of Heat Shock Proteins in Pathways of the Innate and Adaptive Immune System

Cited by 149 publications

References 102 publications

Evidence for induction of humoral and cytotoxic immune responses against devil facial tumor disease cells in Tasmanian devils (Sarcophilus harrisii) immunized with killed cell preparations

Evidence for induction of humoral and cytotoxic immune responses against devil facial tumor disease cells in Tasmanian devils (Sarcophilus harrisii) immunized with killed cell preparations

Cross-Presentation of the Oncofetal Tumor Antigen 5T4 from Irradiated Prostate Cancer Cells—A Key Role for Heat-Shock Protein 70 and Receptor CD91

Gut epithelial inducible heat-shock proteins and their modulation by diet and the microbiota

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