Impact of IL-2 and IL-2R SNPs on Proliferation and Tumorkilling 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 throughin vitro techniques using peripheral blood collected from patients. However, cancer patients generally havepoor immunological function. Thus using patient T cells, which have reduced in vitro proliferative capabilitiesand less tumor cell killing activity to generate lymphokine-activated killer (LAK) cells, fails to achieve optimalclinical 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 singlenucleotide polymorphisms (SNP) in the IL-2 and IL-2R genes. IL-2 and IL-2R SNPs were analyzed using HRMPCR.LAK cells were derived from peripheral blood mononuclear cells by culturing with IL-2. The frequencyand tumor-killing activity of LAK cells in each group were analyzed by flow cytometry and tumor cell killingassays, respectively. Regarding polymorphisms at IL-2-330 (rs2069762) T/G, LAK cells from GG donors hadsignificantly 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 weresignificantly 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 allogeneicLAK cell immunotherapy.