Oxaliplatin regulates expression of stress ligands in ovarian cancer cells and modulates their susceptibility to natural killer cell-mediated cytotoxicity

• Published in: International immunology 2015-12, Vol.27 (12), p.621-632
• Main Authors: Siew, Yin-Yin, Neo, Soek-Ying, Yew, Hui-Chuing, Lim, Shun-Wei, Ng, Yi-Cheng, Lew, Si-Min, Seetoh, Wei-Guang, Seow, See-Voon, Koh, Hwee-Ling
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Cell Line, Tumor; Combined Modality Therapy; Cytotoxicity, Immunologic; Female; Gene Expression Regulation, Neoplastic - drug effects; GPI-Linked Proteins - genetics; GPI-Linked Proteins - metabolism; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - metabolism; Humans; Immunotherapy, Adoptive; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Killer Cells, Natural - transplantation; Organoplatinum Compounds - pharmacology; Ovarian Neoplasms - immunology; Ovarian Neoplasms - therapy; Receptors, TNF-Related Apoptosis-Inducing Ligand - genetics; Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism; Receptors, Virus - genetics; Receptors, Virus - metabolism; Stress, Physiological - drug effects
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxv041

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.