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http://dx.doi.org/10.7314/APJCP.2014.15.18.7965

Impact of IL-2 and IL-2R SNPs on Proliferation and Tumor-killing Activity of Lymphokine-Activated Killer Cells from Healthy Chinese Blood Donors  

Li, Yan (Molecular Oncology Department of Cancer Research Institution, The First Affiliated Hospital of China Medical University)
Meng, Fan-Dong (Molecular Oncology Department of Cancer Research Institution, The First Affiliated Hospital of China Medical University)
Tian, Xin (Molecular Oncology Department of Cancer Research Institution, The First Affiliated Hospital of China Medical University)
Sui, Cheng-Guang (Molecular Oncology Department of Cancer Research Institution, The First Affiliated Hospital of China Medical University)
Liu, Yun-Peng (Oncology, The First Affiliated Hospital of China Medical University)
Jiang, You-Hong (Molecular Oncology Department of Cancer Research Institution, The First Affiliated Hospital of China Medical University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.18, 2014 , pp. 7965-7970 More about this Journal
Abstract
One of the goals of tumor immunotherapy is to generate immune cells with potent anti-tumor activity through in vitro techniques using peripheral blood collected from patients. However, cancer patients generally have poor immunological function. Thus using patient T cells, which have reduced in vitro proliferative capabilities and less tumor cell killing activity to generate lymphokine-activated killer (LAK) cells, fails to achieve optimal clinical efficacy. Interleukin-2 (IL-2) is a potent activating cytokine for both T cells and natural killer cells. Thus, this study aimed to identify optimal donors for allogeneic LAK cell immunotherapy based on single nucleotide polymorphisms (SNP) in the IL-2 and IL-2R genes. IL-2 and IL-2R SNPs were analyzed using HRM-PCR. LAK cells were derived from peripheral blood mononuclear cells by culturing with IL-2. The frequency and tumor-killing activity of LAK cells in each group were analyzed by flow cytometry and tumor cell killing assays, respectively. Regarding polymorphisms at IL-2-330 (rs2069762) T/G, LAK cells from GG donors had significantly greater proliferation, tumor-killing activity, and IFN-${\gamma}$ production than LAK cells from TT donors (P<0.05). Regarding polymorphisms at IL-2R rs2104286 A/G, LAK cell proliferation and tumor cell killing were significantly greater in LAK cells from AA donors than GG donors (P<0.05). These data suggest that either IL-2-330(rs2069762)T/G GG donors or IL-2R rs2104286 A/G AA donors are excellent candidates for allogeneic LAK cell immunotherapy.
Keywords
NK; LAK; IL-2-330 (rs2069762)T/G; IL-2R (rs2104286)A/G; blood donors; killer cells;
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1 Ainiding G, Kawano Y, Sato S, et al (2014). Interleukin 2 receptor $\alpha$ chain gene polymorphisms and risks of multiple sclerosis and neuromyelitis optica in southern Japanese. J Neurol Sci, 337, 147-50.   DOI
2 Archimbaud E, Bailly M, Dore JF (1991). Inducibility of lymphokine activated killer (LAK) cells in patients with acute myelogenous leukaemia in complete remission and its clinical relevance. Br J Haematol, 77, 328-34.   DOI
3 Carr EJ, Clatworthy MR, Lowe CE, et al (2009). Contrasting genetic association of IL2RA with SLE and ANCAassociated vasculitis. BMC Med Genet, 10, 22.
4 Bei CH, Bai H, Yu HP, et al (2014). Combined Effects of Six Cytokine Gene Polymorphisms and SNP-SNP Interactions on Hepatocellular Carcinoma Risk in Southern Guangxi, China. Asian Pac J Cancer Prev, 15, 6961-7.   과학기술학회마을   DOI
5 Brady J, Carotta S, Thong RP, et al (2010). The interactions of multiple cytokines control NK cell maturation. J Immunol, 185, 6679-88.   DOI
6 Buckner JH (2010). Mechanisms of impaired regulation by CD4+CD25+FOXP3+ regulatory T cells in human autoimmune diseases. Nat Rev Immunol, 10, 849-59.   DOI   ScienceOn
7 Cui Zhou, Song-Song Jiang, Cui-Yan Wang, et al (2014). Different immunology mechanisms of Phellinus igniarius in inhibiting growth of liver cancer and melanoma cells. Asian Pac J Cancer Prev, 15, 3659-65.   과학기술학회마을   DOI
8 Chan CJ, Andrews DM, McLaughlin NM, et al (2010). DNAM-1/CD155 nteractionspromote cytokine and NK cell-mediated suppression of poorly immunogenicmelanoma metastases. J Immunol, 184, 902-11.   DOI
9 Dendrou CA, Plagnol V, Fung E, et al (2009). Cell-specific protein phenotypes for the autoimmune locus IL2RA using a genotype-selectable human bioresource. Nat Genet , 41, 1011-5.   DOI
10 Feriazzo G, Moretta L (2014). Dendritic cell editing by natural killer cells. Crit Rev Oncog, 19, 67-75.   DOI
11 Kelly JM, Darcy PK, Markby JL, et al (2002). Induction of tumor-specific T cell memory by NK cell-mediated tumor rejection. Nat Immunol, 3, 83-90.
12 Grimm EA, Mazumder A, Zhang HZ, et al (1982). Lymphokineactivated killer cell phenomenon.Lysis of natural killerresistant fresh solid tumor cells by Interleukin 2-activated autologous human peripheral blood lymphocytes. J Exp Med, 155, 1823-41.   DOI   ScienceOn
13 Hoffmann SC, Stanley EM, Darrin Cox E, et al (2001). Association of cytokine polymorphic inheritance and in vitro cytokine production in anti-CD3/CD28- stimulated peripheral blood lymphocytes.Transplantation, 72, 1444-50.   DOI
14 John S, Turner D, Donn R, et al (1998). Two novel biallelic polymorphisms in the IL-2 gene. Eur J Immunogenet, 25, 419-20.   DOI
15 Lanier LL, Sun JC (2009). Natural killer cells remember:An evolutionary bridge between innate and adaptive immunity? Eur J Immunol, 39, 2059-64.   DOI   ScienceOn
16 Kimura H, Iizasa T, Ishikawa A, Shingyouji M.Yoshino M, Kimura KM, et al (2008). Prospective phase II study of postsurgical adjuvant chemo-immunotherapy using autologous dendritic cells and activated killer cells from tissue culture of tumor-draining lymph nodes in primary lung cancer patients. Anticancer Res, 28, 1229-38.
17 Koh CY, Blazar BR, George T, et al (2001). Augmentation of antitumor effects by NK cell inhibitory receptor blockade in vitro and in vivo. Blood, 97, 3132-7.   DOI
18 Imai K, Matsuyama S, Miyake S, et al (2000). Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence:An 11-year follow-up study of a general population. Lancet, 356, 1795-9.   DOI   ScienceOn
19 Lomonaco E, Tremante E, Cerboni C, et al (2011). Human leukocyteantigen E Contributes to protect tumor cells from lysis by natural killercells. Neoplasia, 13, 822-30.   DOI
20 Ruggeri L, Mancusi A, Burchielli E, et al (2007). Natural killer cell alloreactivity in a allogeneic hematopoietic transplantation. Curr Opin Oncol, 19, 142-7.   DOI
21 Lowe CE, Cooper JD, Brusko T, et al (2007). Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes. Nat Genet, 39, 1074-82.   DOI   ScienceOn
22 Malek TR (2003). The main function of IL-2 is to promote the development of T regulatory cells. J Leukoc Biol, 74, 961-5.   DOI
23 Maier LM, Lowe CE, Cooper J, et al (2009). IL-2RA genetic heterogeneity in multiple sclerosis and type 1 diabetes susceptibility and soluble interleukin-2 receptor production. PLoS Genet, 5, 1000322.   DOI
24 Togawa S, Joh T, Itoh M, et al (2005). Interleukin-2 gene polymorphisms associated with increased risk of gastric atrophy from Helicobacter pylori infection. Helicobacter, 10, 172-8.   DOI   ScienceOn
25 Shubina IZ, Demidov LV, Chikileva IO, et al (2008). LAK immunotherapy in clinical studies. Atlas Effectors of Anti-Tumor Immunity. Springer, 101-10.
26 Smyth DJ, Plagnol V, Walker NM, et al (2008). Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med, 359, 2767-77.   DOI   ScienceOn
27 Srivastava S, Lundqvist A, Childs RW (2008). Natural killer cell immunotherapy for cancer:a new hope. Cytotherapy, 10, 775-83.   DOI   ScienceOn
28 Waldmann TA (2006). The biology of interleukin-2 and interleukin-15:Implications for cancer therapy and vaccinedesign. Nat Rev Immunol, 6, 595-601.   DOI   ScienceOn
29 Wang R, Ciardelli TL, Russell JH (1997). Partial signaling by cytokines:Cytokine regulation of cell cycle and Fasdependent, activation-induced death in CD4+subsets. Cell Immunol, 182, 152-60.   DOI
30 Wang X, Ricker M, Garcia KC (2005). Structure of the quaternary complex of interleukin-2 with its alpha, beta, and gamma receptors. Science, 310, 1159.   DOI
31 Waldmann H (2006). Immunology:protection and privilege. Nature, 442, 987-8.   DOI
32 Erhan Aysan, Omer Faruk Bayrak, Esra Aydemir, et al (2013). cancer preventive effects of whole cell type immunization against mice Ehrlich tumors. Asian Pac J Cancer Prev, 14, 3515-9.   과학기술학회마을   DOI