Heat Shock Proteins (HSP): Future Trends in Cancer Immunotherapy

Abstract

Heat Shock Proteins (HSPs) are a large family of highly conserved proteins involved in assisting protein folding and unfolding in the cells. HSPs are expressed constitutively as well as inducibly and, interacting with antigen presenting cells, induce the expression of various cytokines and chemokines as well as the maturation and migration of dendritic cells, thus acting themselves as cytokines. HSP-chaperoned antigenic peptides are also generated within the tumor cells. Such chaperoned peptides are released in the extra cellular medium with an association of HSPs by cell stress, death or tumor cell lyses. HSP-peptide complexes from extra cellular medium are taken up by antigen presenting cells through CD91 receptor and are represented or cross-presented by their MHC class I molecules for specific anti-tumor immune response. In addition, HSPs expressed on the cell surface of tumor cells stimulate αβ T-cells and γδ T-cells as well as natural killer (NK) cells that are first-line defense mechanisms. In this manner, HSPs have the ability to stimulate both arms of the effecter mechanism of the immune system. These unique immunological attributes of HSPs are presently becoming the basis for tumor immunotherapy. Tumor-derived HSP-peptide complexes have been demonstrated to serve as anti-tumor vaccines. To date various approaches of vaccination using HSPs have been developed and tested clinically. These HSP-based vaccine approaches can be combined with hyperthermia and CTLA-4 blockade to enhance their anti-tumor potentiality.