期刊
JOURNAL OF IMMUNOTHERAPY
卷 41, 期 6, 页码 274-283出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CJI.0000000000000229
关键词
memory stem T cell; adoptive transfer; interleukin-21; STAT3
资金
- Introduction of Innovative R&D Team Program of Guangdong Province [2009010058]
- Natural Science Foundation of China [81561128007]
- US NIH [81561128007]
- Important Key Program of Natural Science Foundation of China [81590765]
- National Special Research Program for Important Infectious Diseases [2013ZX10001004]
- Joint-innovation Program in Healthcare for Special Scientific Research Projects of Guangzhou [201508020256]
- Industry-Academia-Research planning project of Guangdong [2014B090904065]
- China Postdoctoral Science Foundation [2016M600700]
Memory stem T (T-SCM) cells, a new subset of memory T cells with self-renewal and multipotent capacities, are considered as a promising candidates for adoptive cellular therapy. However, the low proportion of human T-SCM cells in total CD8(+) T cells limits their utility. Here, we aimed to induce human CD8(+) T-SCM cells by stimulating naive precursors with interleukin-21 (IL-21). We found that IL-21 promoted the generation of T-SCM cells, described as CD45RA(+)CD45RO(-)CD62L(+)CCR7(+)CD122(+)CD95(+) cells, with a higher efficiency than that observed with other common -chain cytokines. Upon adoptive transfer into an A375 melanoma mouse model, these lymphocytes mediated much stronger antitumor responses. Further mechanistic analysis revealed that IL-21 activated the Janus kinase signal transducer and activator of transcription 3 pathway by upregulating signal transducer and activator of transcription 3 phosphorylation and consequently promoting the expression of T-bet and suppressor of cytokine signaling 1, but decreasing the expression of eomesodermin and GATA binding protein 3. Our findings provide novel insights into the generation of human CD8(+) T-SCM cells and reveal a novel potential clinical application of IL-21.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据