Heat Shock Proteins, Autoimmunity, and Cancer Treatment

Abstract

Heat shock proteins (HSPs) have been linked to the therapy of both cancer and inflammatory diseases, approaches that utilize contrasting immune properties of these proteins. It would appear that HSP family members Hsp60 and Hsp70, whether from external sources or induced locally during inflammation, can be processed by antigen-presenting cells and that HSP-derived epitopes then activate regulatory T cells and suppress inflammatory diseases. These effects also extend to the HSP-rich environments of cancer cells where elevated HSP concentrations may participate in the immunosuppressive tumor milieu. However, HSPs can also be important mediators of tumor immunity. Due to their molecular chaperone properties, some HSPs can bind tumor-specific peptides and deliver them deep into the antigen-processing pathways of antigen-presenting cells (APCs). In this context, HSP-based vaccines can activate tumor-specific immunity, trigger the proliferation and CTL capabilities of cancer-specific CD8+ T cells, and inhibit tumor growth. Further advances in HSP-based anticancer immunotherapy appear to involve improving the properties of the molecular chaperone vaccines by enhancing their antigen-binding properties and combating the immunosuppressive tumor milieu to permit programming of active CTL capable of penetrating the tumor milieu and specifically targeting tumor cells.