title: HSP90 and Immune Modulation in Cancer.
abstract: Heat-shock protein 90 (HSP90) is a highly conserved molecular chaperone that plays prominent functional roles in nearly all aspects of cell biology. As a chaperone, it interacts with literally hundreds of "clients," many of which are important drivers, regulators, and promoters of cancer. Thus, HSP90 is a high-value target in the development of anticancer therapeutics. Despite its popularity, our overall knowledge of HSP90 in immune function has lagged behind its well-recognized tumor-supportive roles. The use of inhibitors of HSP90 as chemical biological probes has been invaluable in revealing important roles for the chaperone in multiple aspects of immune function. Given this critical link, we must now consider the question of how immune outcomes may be affected by the HSP90 inhibitors currently in clinical development for the treatment of cancer. This chapter will review some of the immunological aspects of HSP90 function in terms of its intracellular and extracellular roles in antigen presentation, immune effector cell tasks, and regulation of inflammatory processes. This review will further examine the value of HSP90 inhibitors within the context of cancer immunotherapy and will discuss how these drugs might be optimally utilized in combination with immune stimulatory approaches against cancer.
authors.affiliation: Department of Neurosurgery, University of Colorado Denver, Aurora, Colorado, USA. Electronic address: michael.graner@ucdenver.edu.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Graner
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000276:immunology; D055354:Exosomes / Q000276:immunology / Q000378:metabolism; D005110:Extracellular Space / Q000276:immunology / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D018869:Heat-Shock Response / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D056747:Immunomodulation; D007249:Inflammation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy*
chemical_list: D000954:Antigens, Surface; D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D008562:Membrane Glycoproteins; C053387:endoplasmin
keywords: Antigen presentation; HSP90; Immunotherapy; Inflammation; Inhibitor; Tumor immunity