title: Impact of IL-2 and IL-2R SNPs on proliferation and tumor- killing activity of lymphokine-activated killer cells from healthy chinese blood donors.
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-γ 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.
authors.affiliation: Molecular Oncology Department of Cancer Research Institution, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province,ChinaE-mail : jiang_youhong58@126.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Fan-Dong
authors.initials: FD
authors.lastname: Meng
authors.forename: Xin
authors.initials: X
authors.lastname: Tian
authors.forename: Cheng-Guang
authors.initials: CG
authors.lastname: Sui
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Liu
authors.forename: You-Hong
authors.initials: YH
authors.lastname: Jiang
mesh_terms: D000328:Adult; D001782:Blood Donors; D049109:Cell Proliferation; D002681:China; D003602:Cytotoxicity, Immunologic; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: C508594:IL2 protein, human; D007376:Interleukin-2; D015375:Receptors, Interleukin-2