title: Anticancer metal drugs and immunogenic cell death.
abstract: Conventional chemotherapeutics, but also innovative precision anticancer compounds, are commonly perceived to target primarily the cancer cell compartment. However, recently it was discovered that some of these compounds can also exert immunomodulatory activities which might be exploited to synergistically enhance their anticancer effects. One specific phenomenon of the interplay between chemotherapy and the anticancer immune response is the so-called "immunogenic cell death" (ICD). ICD was discovered based on a vaccination effect exerted by cancer cells dying from pretreatment with certain chemotherapeutics, termed ICD inducers, in syngeneic transplantation mouse models. Interestingly, only a minority of drugs is able to trigger ICD without a clear-cut relation to chemical structures or their primary modes-of-action. Nevertheless, generation of reactive oxygen species (ROS) and induction of endoplasmic reticulum (ER) stress are clearly linked to ICD. With regard to metal drugs, oxaliplatin but not cisplatin is considered a bona fide ICD inducer. Taken into account that several experimental metal compounds are efficient ROS and ER stress mediators, presence of potent ICD inducers within the plethora of novel metal complexes seems feasible and has occasionally been reported. In the light of recent successes in cancer immunotherapy, here we review existing literature regarding anticancer metal drugs and ICD induction. We recommend a more profound investigation of the immunogenic features of experimental anticancer metal drugs.
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Waehringerstr. 42, A-1090 Vienna, Austria; Research Platform "Translational Cancer Therapy Research", University of Vienna and Medical University of Vienna, Vienna, Austria.
authors.forename: Alessio
authors.initials: A
authors.lastname: Terenzi
authors.affiliation: Department of Medicine I, Institute of Cancer Research and Comprehensive Cancer Center, Medical University Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Pirker
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Waehringerstr. 42, A-1090 Vienna, Austria; Research Platform "Translational Cancer Therapy Research", University of Vienna and Medical University of Vienna, Vienna, Austria.
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
authors.affiliation: Research Platform "Translational Cancer Therapy Research", University of Vienna and Medical University of Vienna, Vienna, Austria; Department of Medicine I, Institute of Cancer Research and Comprehensive Cancer Center, Medical University Vienna, Borschkegasse 8a, A-1090 Vienna, Austria. Electronic address: walter.berger@meduniwien.ac.at.
authors.forename: Walter
authors.initials: W
authors.lastname: Berger
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000276:immunology; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000652:urine*; D000077150:Oxaliplatin; D017382:Reactive Oxygen Species / Q000276:immunology*
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D017382:Reactive Oxygen Species; D000077150:Oxaliplatin
keywords: Anticancer metal drugs; Cisplatin; Immunogenic cell death; Oxaliplatin