title: The regulatory effect of UL-16 binding protein-3 expression on the cytotoxicity of NK cells in cancer patients.
abstract: The activating immunoreceptor NKG2D (natural killer group 2, member D) and its ligands play important roles in the innate and adaptive immune responses. UL16-binding protein 3 (ULBP3), an NKG2D ligand, is overexpressed on certain epithelial tumor cells. In this study, we investigated the effect of ULBP3 expression on the cytotoxic activity of natural killer (NK) cells. ULBP3 were measured by flow cytometry analysis, immunohistochemistry, and time-resolved fluoroimmunoassay. The cytotoxicity of NK cells was determined with the lactate dehydrogenase release assay. We found that ULBP3 was overexpressed on tumor cell lines and tumor tissues. Serum from cancer patients, but not from healthy donors, contained elevated levels of soluble ULBP3 (sULBP3). Importantly, high expression of ULBP3 on the cell surface of tumor cells augmented NKG2D-mediated NK cell cytotoxicity. However, low levels of sULBP3 (<15 ng/ml) weakened the cytotoxicity of NK cells by decreasing NKG2D expression on NK cells. Further analysis showed that serum samples from most cancer patients (>70%) contained the low level of sULBP3. Our results demonstrate that tumor cells express surface and soluble ULBP3, which regulate NK cell activity. Thus, ULBP3 is a potential therapeutic target for improving the immune response against cancer.
authors.affiliation: 1] Department of Nuclear Medicine, The Hospital Affiliated to Jiangsu University, Zhenjiang, China [2] Institute of Oncology, The Hospital Affiliated to Jiangsu University, Zhenjiang, China [3].
authors.forename: Xiao
authors.initials: X
authors.lastname: Mou
authors.affiliation: 1] Department of Nuclear Medicine, The Hospital Affiliated to Jiangsu University, Zhenjiang, China [2] Institute of Oncology, The Hospital Affiliated to Jiangsu University, Zhenjiang, China [3].
authors.forename: Yuepeng
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: 1] Department of anesthesiology, The Hospital Affiliated to Jiangsu University, Zhenjiang, China [2].
authors.forename: Peng
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Nuclear Medicine, The Hospital Affiliated to Jiangsu University, Zhenjiang, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: 1] Department of Nuclear Medicine, The Hospital Affiliated to Jiangsu University, Zhenjiang, China [2] Institute of Oncology, The Hospital Affiliated to Jiangsu University, Zhenjiang, China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Xu
authors.affiliation: 1] Department of Nuclear Medicine, The Hospital Affiliated to Jiangsu University, Zhenjiang, China [2] Institute of Oncology, The Hospital Affiliated to Jiangsu University, Zhenjiang, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Liu
authors.affiliation: 1] Department of Nuclear Medicine, The Hospital Affiliated to Jiangsu University, Zhenjiang, China [2] Institute of Oncology, The Hospital Affiliated to Jiangsu University, Zhenjiang, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zheng
authors.affiliation: Department of Nuclear Medicine, The Hospital Affiliated to Jiangsu University, Zhenjiang, China.
authors.forename: Guoyue
authors.initials: G
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 1] Department of Nuclear Medicine, The Hospital Affiliated to Jiangsu University, Zhenjiang, China [2] Institute of Oncology, The Hospital Affiliated to Jiangsu University, Zhenjiang, China.
authors.forename: Deyu
authors.initials: D
authors.lastname: Chen
authors.affiliation: 1] Department of Nuclear Medicine, The Hospital Affiliated to Jiangsu University, Zhenjiang, China [2] Institute of Oncology, The Hospital Affiliated to Jiangsu University, Zhenjiang, China.
authors.forename: Chaoming
authors.initials: C
authors.lastname: Mao
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D015536:Down-Regulation; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000378:metabolism*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D058851:GPI-Linked Proteins; D036341:Intercellular Signaling Peptides and Proteins; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D034741:RNA, Small Interfering; C423229:ULBP3 protein, human