Prognosis of ovarian cancer is associated with effector memory CD8(+) T cell accumulation in ascites, CXCL9 levels and activation-triggered signal transduction in T cells.
Prognosis of ovarian cancer is associated with effector memory CD8(+) T cell accumulation in ascites, CXCL9 levels and activation-triggered signal transduction in T cells.
复制标题
DOI：
10.1080/2162402x.2018.1424672
复制
发表时间：
2018
期刊：
影响因子：
7.2
通讯作者：
Huber M
中科院分区：
文献类型：
--
作者：
Lieber S;Reinartz S;Raifer H;Finkernagel F;Dreyer T;Bronger H;Jansen JM;Wagner U;Worzfeld T;Müller R;Huber M
CD8+T细胞在肿瘤内的聚集与高级别浆液性卵巢癌患者的生存有关，但目前尚不清楚哪些CD8+T细胞亚群参与了这种作用，以及它们是如何受到腹膜肿瘤微环境的影响的。在这里，我们提供了一个证据，证明了长期无复发生存，腹水(腹水)中CD8+效应记忆T(TEM)细胞的积累，以及作为主要来源的巨噬细胞产生的CD8+TEM吸引趋化因子CXCL9的水平之间的功能联系。我们还提出了一种新的机制，即肿瘤微环境可能导致T细胞功能障碍和生存期缩短，即关键信号蛋白表达水平降低，包括STAT5B、PLCγ1和NFATC2。因此，腹水中CD8+细胞、CXCL9水平和关键信号转导蛋白的表达可能是衡量免疫治疗有效性的重要生物标志物，并有可能成为治疗的靶点。
The accumulation of intratumoral CD8+ T cells is associated with the survival of high grade serous ovarian carcinoma patients, but it is unclear which CD8+ T cell subsets contribute to this effect and how they are affected by the peritoneal tumor microenvironment. Here, we provide evidence for a functional link between long relapse-free survival, accumulation of CD8+ effector memory T (TEM) cells in peritoneal effusion (ascites), and the level of the CD8+ TEM attracting chemokine CXCL9, produced by macrophages as a major source. We also propose a novel mechanism by which the tumor microenvironment could contribute to T cell dysfunction and shorter survival, i.e., diminished expression levels of essential signaling proteins, including STAT5B, PLCγ1 and NFATc2. CD8+ TEM cells in ascites, CXCL9 levels and the expression of crucial signal transduction proteins may therefore be important biomarkers to gauge the efficiency of immune therapies and potentially represent therapeutic targets.