AUTHOR=Shevtsov Maxim , Multhoff Gabriele TITLE=Heat Shock Protein–Peptide and HSP-Based Immunotherapies for the Treatment of Cancer JOURNAL=Frontiers in Immunology VOLUME=7 YEAR=2016 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2016.00171 DOI=10.3389/fimmu.2016.00171 ISSN=1664-3224 ABSTRACT=

Intracellular residing heat shock proteins (HSPs) with a molecular weight of approximately 70 and 90 kDa function as molecular chaperones that assist folding/unfolding and transport of proteins across membranes and prevent protein aggregation after environmental stress. In contrast to normal cells, tumor cells have higher cytosolic heat shock protein 70 and Hsp90 levels, which contribute to tumor cell propagation, metastasis, and protection against apoptosis. In addition to their intracellular chaperoning functions, extracellular localized and membrane-bound HSPs have been found to play key roles in eliciting antitumor immune responses by acting as carriers for tumor-derived immunogenic peptides, as adjuvants for antigen presentation, or as targets for the innate immune system. The interaction of HSP–peptide complexes or peptide-free HSPs with receptors on antigen-presenting cells promotes the maturation of dendritic cells, results in an upregulation of major histocompatibility complex class I and class II molecules, induces secretion of pro- and anti-inflammatory cytokines, chemokines, and immune modulatory nitric oxides, and thus integrates adaptive and innate immune phenomena. Herein, we aim to recapitulate the history and current status of HSP-based immunotherapies and vaccination strategies in the treatment of cancer.