title: Oxaliplatin regulates expression of stress ligands in ovarian cancer cells and modulates their susceptibility to natural killer cell-mediated cytotoxicity.
abstract: Selected cytotoxic chemicals can provoke the immune system to recognize and destroy malignant tumors. Most of the studies on immunogenic cell death are focused on the signals that operate on a series of receptors expressed by dendritic cells to induce tumor antigen-specific T-cell responses. Here, we explored the effects of oxaliplatin, an immunogenic cell death inducer, on the induction of stress ligands and promotion of natural killer (NK) cell-mediated cytotoxicity in human ovarian cancer cells. The results indicated that treatment of tumor cells with oxaliplatin induced the production of type I interferons and chemokines and enhanced the expression of major histocompatibility complex class I-related chains (MIC) A/B, UL16-binding protein (ULBP)-3, CD155 and TNF-related apoptosis-inducing ligand (TRAIL)-R1/R2. Furthermore, oxaliplatin but not cisplatin treatment enhanced susceptibility of ovarian cancer cells to NK cell-mediated cytolysis. In addition, activated NK cells completely abrogated the growth of cancer cells that were pretreated with oxaliplatin. However, cancer cells pretreated with the same concentration of oxaliplatin alone were capable of potentiating regrowth over a period of time. These results suggest an advantage in combining oxaliplatin and NK cell-based therapy in the treatment of ovarian cancer. Further investigation on such potential combination therapy is warranted.
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Singapore.
authors.forename: Yin-Yin
authors.initials: YY
authors.lastname: Siew
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Singapore.
authors.forename: Soek-Ying
authors.initials: SY
authors.lastname: Neo
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Singapore.
authors.forename: Hui-Chuing
authors.initials: HC
authors.lastname: Yew
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Singapore.
authors.forename: Shun-Wei
authors.initials: SW
authors.lastname: Lim
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Singapore.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Ng
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Singapore.
authors.forename: Si-Min
authors.initials: SM
authors.lastname: Lew
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Singapore.
authors.forename: Wei-Guang
authors.initials: WG
authors.lastname: Seetoh
authors.affiliation: Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore Affiliated National University Cancer Institute, National University Health System, Singapore 119074, Singapore.
authors.forename: See-Voon
authors.initials: SV
authors.lastname: Seow
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Singapore phakohhl@nus.edu.sg.
authors.forename: Hwee-Ling
authors.initials: HL
authors.lastname: Koh
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003602:Cytotoxicity, Immunologic; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016219:Immunotherapy, Adoptive; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy*; D000077150:Oxaliplatin; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D036341:Intercellular Signaling Peptides and Proteins; C099187:MHC class I-related chain A; C098080:MICB antigen; D009944:Organoplatinum Compounds; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D011991:Receptors, Virus; C423229:ULBP3 protein, human; C066100:poliovirus receptor; D000077150:Oxaliplatin
keywords: cytotoxicity; immunogenic cell death; natural killer cells; ovarian cancer; oxaliplatin; stress ligands