Downregulation of IFNG in CD4(+) T cells in lung cancer through hypermethylation: a possible mechanism of tumor-induced immunosuppression.
Downregulation of IFNG in CD4(+) T cells in lung cancer through hypermethylation: a possible mechanism of tumor-induced immunosuppression.
复制标题
肺癌 CD4 T 细胞中 IFNG 通过高甲基化下调：肿瘤诱导免疫抑制的可能机制
DOI：
10.1371/journal.pone.0079064
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Pan S
中科院分区：
文献类型：
--
作者：
Wang F;Xu J;Zhu Q;Qin X;Cao Y;Lou J;Xu Y;Ke X;Li Q;Xie E;Zhang L;Sun R;Chen L;Fang B;Pan S
肿瘤存活率与患者的免疫反应显着相关。 IFNG 在肿瘤宿主反应中发挥重要作用，在肺癌中经常观察到 IFNG 表达降低。研究表明，CpG 岛高甲基化在 IFNG 基因表达的转录沉默中发挥着关键作用。然而，对于甲基化改变的分子机制以及肿瘤微环境是否对 DNA 甲基化和 IFNG 产生有影响，人们的了解还有限。在当前的研究中，我们证明肺癌患者的血浆和细胞内 IFNG 水平显着降低。 CD4+ T细胞中IFNG启动子的高甲基化与血浆IFNG呈负相关。来自健康个体的 CD4+ T 细胞与 SPC-A1 细胞共培养，激活后产生较低水平的 IFNG，DNA 甲基转移酶 (DNMT) 表达升高，并表现出 IFNG 启动子的高甲基化。总之，与肺癌细胞共培养的CD4+T细胞的IFNG表达降低与IFNG启动子高甲基化有关。我们的研究表明，肺癌细胞与CD4+ T细胞之间的相互作用诱导CD4+ T细胞中DNMT表达和IFNG启动子高甲基化，这可能是肿瘤诱导免疫抑制的重要机制。
Tumor survival is significantly correlated with the immune response of patients. IFNG plays an important role in the tumor host response and decreased IFNG expression is often observed in lung cancer. Studies have shown that CpG island hypermethylation plays a critical role in transcriptional silencing of IFNG gene expression. However, there is limited understanding regarding the molecular mechanisms of altered methylation, and whether the tumor microenvironment has any effect on DNA methylation and IFNG production. In the current study, we demonstrate that plasma and intra-cellular IFNG levels are significantly lower in lung cancer patients. Hypermethylation of the IFNG promoter in CD4+ T cells and plasma IFNG was negatively correlated. CD4+ T cells from healthy individuals co-cultured with SPC-A1 cells generated lower levels of IFNG after activation, elevated expression of DNA methyltransferases (DNMTs), and exhibited hypermethylation of the IFNG promoter. In conclusion, decreased IFNG expression of CD4+ T cells co-cultured with lung cancer cell is associated with IFNG promoter hypermethylation. Our study suggests that interaction between lung cancer cells and CD4+ T cells induces DNMT expression and IFNG promoter hypermethylation in CD4+ T cell, which may serve as an important mechanism of tumor-induced immunosuppression.
登录
查看更多内容
影响因子：
4.4
作者：
Cohen, Carla J.;Crome, Sarah Q.;Levings, Megan K.
通讯作者：
Levings, Megan K.
影响因子：
11.2
作者：
Ehrich, Mathias;Field, John K.;van den Boom, Dirk
通讯作者：
van den Boom, Dirk
影响因子：
4.7
作者：
Lantry, LE;Zhang, ZQ;You, M
通讯作者：
You, M
影响因子：
32.4
作者：
DIGHE, AS;RICHARDS, E;SCHREIBER, RD
通讯作者：
SCHREIBER, RD
影响因子：
5.8
作者：
Alshaker HA;Matalka KZ
通讯作者：
Matalka KZ