Impact of IL-2 and IL-2R SNPs on proliferation and tumor- killing activity of lymphokine-activated killer cells from healthy chinese blood donors

Asian Pac J Cancer Prev. 2014;15(18):7965-70. doi: 10.7314/apjcp.2014.15.18.7965.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Donors
  • Cell Proliferation*
  • China
  • Cytotoxicity, Immunologic*
  • Female
  • Healthy Volunteers
  • Humans
  • Interleukin-2 / genetics*
  • Killer Cells, Lymphokine-Activated / physiology*
  • Leukocytes, Mononuclear / immunology
  • Male
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / pathology*
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, Interleukin-2 / genetics*
  • Tumor Cells, Cultured

Substances

  • IL2 protein, human
  • Interleukin-2
  • Receptors, Interleukin-2