Heat Shock Proteins in Cancer Immunotherapy

Figure 2

Overview of pathways in tumor antigen cross-presentation by the HSPs to the APCs. Cancer cells display limited surface peptides or antigens which are released into the extracellular milieu. These antigens are recognized by HSPs through HSP-receptors, such as SRECI and LOX-1. The HSP peptide complex may be either engulfed into the DCs through CD91 receptor-mediated endocytosis or recognized by the cognate receptors on the surface of these DCs, resulting in their activation. This leads to a cascade of subsequent innate and adaptive immunological responses against cancer cells. The activated DCs activate the γδ T cells and NK T cells which may facilitate the lysis of the cancer cells. These DCs also produce inflammatory cytokines, chemokines, and nitric oxide. The activation of APCs results in the recognition and killing of cancer cells through cytotoxic CD8+ T-lymphocytes response. The lysis of cancer cells releases cancer antigens into the extracellular milieu leading to the formation of memory CD8+ T cells. The cross-presentation of HSP peptide complex to APCs is therefore an effective process bridging innate and adaptive immune response and mounting an optimal anticancer immunity. The inactive DCs/CD8+ T cells are represented in light color while the activated cells are represented in dark color. This illustration has been created with Biorender.com. DC-dendritic cells.