癌症研究
淋巴瘤
T细胞
弥漫性大B细胞淋巴瘤
生发中心
B细胞淋巴瘤
幼稚B细胞
FOXP3型
BCL6公司
细胞
调节性B细胞
免疫系统
CD8型
医学
T细胞淋巴瘤
细胞生物学
作者
Zhi Zhang Yang,Anne J. Novak,Steven C. Ziesmer,Thomas E. Witzig,Stephen M. Ansell
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2009-07-01
卷期号:69 (13): 5522-5530
被引量:124
标识
DOI:10.1158/0008-5472.can-09-0266
摘要
Using biopsy specimens from patients with B-cell non-Hodgkin's lymphoma, we observed a significantly low frequency of T(H)17 cells, including several samples with no detectable amount of interleukin (IL)-17-producing cells present in the tumor microenvironment. We found that, in the absence of lymphoma B cells, treatment with IL-1beta/IL-6 or lipopolysaccharide (LPS) enhanced IL-17 expression in CD4(+) T cells and this enhancement was attenuated when CD4(+) T cells were cocultured with lymphoma B cells. Blockade of CD27-CD70 or CD28-CD80/86 interactions by anti-CD70 or anti-CD80/86 antibodies restored LPS-mediated induction of IL-17 expression in CD4(+) T cells cocultured with lymphoma B cells. Because a subset of lymphoma B cells express IL-2 and given that IL-2 signaling is critically important in the development of regulatory T (T(reg)) cells, we tested the role of IL-2 signaling in T(H)17 cell development. We found that treatment with anti-IL-2 antibody to interrupt IL-2 signaling significantly inhibited Foxp3 expression in CD4(+) T cells. In contrast, interruption of IL-2 signaling up-regulated IL-17 expression in CD4(+) T cells and restored lymphoma-mediated down-regulation of IL-17-producing cells. Furthermore, the reversal of T(reg) cell activity by LPS or CpG-A resulted in an enhancement of IL-17-producing cells. Taken together, our study indicated that lymphoma B cells play an important role in skewing the balance between T(reg) and T(H)17 cells resulting in the establishment of a profoundly inhibitory tumor microenvironment.
科研通智能强力驱动
Strongly Powered by AbleSci AI