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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)
  • Published : 2014.10.11

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.

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