Heat shock protein HSP60 and the perspective for future using as vaccine antigens

Abstract

Heat Shock Proteins (HSPs) are widely spread in nature, highly conserved proteins, found in all prokaryotic and eukaryotic cells. HSPs have been classified in 10 families, one of them is the HSP60 family. HSP60 function in the cytoplasm as ATP-dependent molecular chaperones by assisting the folding of newly synthesised polypeptides and the assembly of multiprotein complexes. There is a large amount of evidence which demonstrate that HSP60 is expressed on the cell surface. Especially in bacteria the expression on the surface occurs constitutively and increases remarkably during host infection. HSP60 also play an important role in biofilm formation. In the extracellular environment, HSP60 alone or with self or microbial proteins can acts not only as a link between immune cells, but also as a coordinator of the immune system activity. This protein could influence the immune system in a different way because they act as an antigen, a carrier of other functional molecules or as a ligand for receptor. They are able to stimulate both cells of the acquired (naïve, effector, regulatory T lymphocyte, B lymphocyte) and the innate (macrophages, monocytes, dendritic cells) immune system. HSPs have been reported to be potent activators of the immune system and they are one of the immunodominant bacterial antigens they could be a good candidate for a subunit vaccine or as an adjuvant.

Focused ultrasound for immuno-adjuvant treatment of pancreatic cancer: An emerging clinical paradigm in the era of personalized oncotherapy

“…One possible mechanism to explain these findings it that thermal ablation delivers sub-lethal heat exposure to peripheral, surviving tumor cells and can thus cause upregulation and surface expression of heat shock proteins (HSPs). HSPs are intracellular molecular chaperones that can bind tumor peptide antigens and have long been recognized as potent stimulators of tumor immunogenicity via antigen-presenting cells of the endogenous immune system (dendritic cells, macrophages, CD4 + T cells) [121–127]. Although studies of HSP expression specific to pancreatic cancer cell lines have not yet been published, preliminary results have been presented, and this topic is being actively pursued [128].…”

Focused ultrasound-aided immunomodulation in glioblastoma multiforme: a therapeutic concept

“…HSPs are intracellular molecular chaperones, able to bind tumor peptide antigens and enhance tumor cell immunogenicity [ 74 – 79 ]. Antigen-presenting cells (APCs; namely DCs, macrophages and CD4 + T helper cells) endocytose the HSP-tumor peptide complex and present the chaperoned peptides directly to tumor-specific CTLs.…”

Can High Intensity Focused Ultrasound Facilitate Immunomodulation in Glioblastoma Multiforme?

“…The latter refers to lengthened survival and immunomodulatory effects of FUS noted in different reports but lacking a proven exact molecular mechanism [11,20,23] . HSP's are known potent immune-stimulants, able to bind tumor peptide antigens and enhance tumor cell immunogenicity [57][58][59][60][61][62] . FUS was shown to up-regulate the expression of HSP70 both in-vitro and ex-vitro [16,24,25] .…”