title: Induction of immunogenic cell death by chemotherapeutic platinum complexes.
abstract: There is compelling evidence suggesting that the immune-modulating effects of many conventional chemotherapeutics, including platinum-based agents, play a crucial role in achieving clinical response. One way in which chemotherapeutics can engage a tumor-specific immune response is by triggering an immunogenic mode of tumor cell death (ICD), which then acts as an "anticancer vaccine". In spite of being a mainstay of chemotherapy, there has not been a systematic attempt to screen both existing and upcoming Pt agents for their ICD ability. A library of chemotherapeutically active Pt agents was evaluated in an in vitro phagocytosis assay, and no correlation between cytotoxicity and phagocytosis was observed. A Pt(II) N-heterocyclic carbene complex was found to display the characteristic hallmarks of a type II ICD inducer, namely focused oxidative endoplasmic reticulum (ER) stress, calreticulin exposure, and both HMGB1 and ATP release, and thus identified as the first small-molecule immuno-chemotherapeutic agent.
authors: Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore (Singapore).
authors: Daniel Yuan Qiang
authors: DY
authors: Wong
authors: Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore (Singapore).
authors: Wendy Wei Fang
authors: WW
authors: Ong
authors: Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore (Singapore). chmawh@nus.edu.sg.|NUS Graduate School of Integrative Sciences and Engineering, 28 Medical Drive, Singapore (Singapore). chmawh@nus.edu.sg.
authors: Wee Han
authors: WH
authors: Ang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D037282:Calreticulin / Q000378:metabolism; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D024243:HMGB1 Protein / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects; D010984:Platinum / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D037282:Calreticulin; D056831:Coordination Complexes; D024243:HMGB1 Protein; D010984:Platinum
keywords: antitumor agents; immuno-chemotherapy; immunogenic cell death; oxidative stress; platinum