Immunogenicity of 56°C and UVC‐treated prostate cancer is associated with release of HSP70 and HMGB1 from necrotic cells

Abstract

These data may be of use in the design of effective non-surgical PCa ablations that combine tumor destruction with long lasting immunity.

Consensus guidelines for the detection of immunogenic cell death

“…121 So far, 3 DAMPs have been attributed a key role in the immunogenic potential of virtually all ICD inducers: the endoplasmic reticulum (ER) chaperone calreticulin (CALR), 34,65,126,[134][135][136] ATP, 66,124,[137][138][139][140][141][142][143] and HMGB1. 41,46,115,116,[144][145][146][147] In addition, many DAMPs have been shown to contribute to the immunogenicity of cell death in a limited amount of experimental scenarios. These include immunostimulatory cytokines like interferon a (IFNa), various chaperones of the heat-shock protein (HSP) family, notably heat shock 70kDa protein 1A (HSPA1A, best known as HSP70) and heat shock protein 90kDa a (cytosolic), class A member 1 (HSP90AA1, best known as HSP90), 65,71,85,90,145,[150][151][152][153] sphingomyelin metabolites (e.g., ceramide and sphingosine-1-phosphate), 154 a plethora of mitochondrial products (e.g., mitochondrial DNA, N-formylated peptides, cardiolipin), [155][156][157] cytosolic components like urate and F-actin, [158][159][160][161] as well as products of the breakdown of the extracellular matrix (e.g., hyaluronan f...…”

“…41,46,115,116,[144][145][146][147] In addition, many DAMPs have been shown to contribute to the immunogenicity of cell death in a limited amount of experimental scenarios. These include immunostimulatory cytokines like interferon a (IFNa), various chaperones of the heat-shock protein (HSP) family, notably heat shock 70kDa protein 1A (HSPA1A, best known as HSP70) and heat shock protein 90kDa a (cytosolic), class A member 1 (HSP90AA1, best known as HSP90), 65,71,85,90,145,[150][151][152][153] sphingomyelin metabolites (e.g., ceramide and sphingosine-1-phosphate), 154 a plethora of mitochondrial products (e.g., mitochondrial DNA, N-formylated peptides, cardiolipin), [155][156][157] cytosolic components like urate and F-actin, [158][159][160][161] as well as products of the breakdown of the extracellular matrix (e.g., hyaluronan fragments). 162,163 CALR gets exposed on the cell surface early in the course of ICD, i.e., before the apoptosis-associated shuffling of phosphatidylserine between the inner and outer leaflet of the plasma membrane.…”

Physical modalities inducing immunogenic tumor cell death for cancer immunotherapy

“…RT has been shown to induce the surface exposure of CRT 14,57 and HSP70, 58 and HMGB1 release. 57,59 Irradiated tumor cells stimulate DC maturation 60 and induce IFNg-producing T cells in vitro and in vivo. 38,61,62 Moreover, mice vaccinated with DCs loaded with irradiated cancer cells are immune to the challenge with live syngeneic cells.…”

“…59 Various molecular determinants and pathways of UVC-light-mediated ICD await further elucidation. The ability of UVC but not UVA or UVB light to induce ICD has been an enigma which remains unexplored.…”

Treatment of fever with traditional Chinese medicine according to Zheng on cancer patients (based on case reports)

“…The treatment could remove heat and dampness, and smooth activities of qi (Brusa et al, 2009). We can give the prescription as Gan-Lu-Xiao-Du-Dan or San-Ren-Tang.…”