PD-1 是T细胞淋巴发育的平抑制剂
Tim Wartewig1,2, Zsuzsanna Kurgyis1,2, Selina Keppler1,2
1Institut für Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universität München, 81675 München, Germany.
Nature
|November 17, 2017
概括
在T细胞淋巴瘤中,编程死亡-1 (PD-1) 通过抵消瘤T细胞受体信号来起瘤抑制作用. 人类T细胞淋巴瘤中频繁发生的PD-1变化凸显了其在癌症治疗中的临床意义.
科学领域:
- 免疫学
- 癌症学
- 分子生物学
背景情况:
- T细胞非霍奇金淋巴瘤是具有不良后果的侵袭性癌症.
- 瘤T细胞受体 (TCR) 信号驱动淋巴瘤的扩散,但对抗瘤抑制剂是未知的.
- 编码PD-1受体的PDCD1被确定为一个关键抑制剂.
研究的目的:
- 研究T细胞淋巴瘤中抗癌TCR信号的细胞内在机制.
- 确定参与T细胞淋巴瘤发展的新型瘤抑制剂.
- 确定PD-1在T细胞淋巴瘤发病中的作用及其临床相关性.
主要方法:
- 人类T细胞淋巴瘤与强制性瘤TCR信号的小鼠模型.
- 在体内全基因组的转子子突变检测.
- 在人类T细胞淋巴瘤中分析PDCD1 (PD-1) 基因缺失.
- 对PTEN,AKT和PKC信号通路的评估.
主要成果:
- 强制性瘤性TCR信号最初扩展T细胞,但被内在机制抵消.
- 已确定PDCD1 (PD-1) 是致癌性T细胞信号传递的主要抑制剂.
- 在超过30%的人类T细胞淋巴瘤中发生PDCD1缺失.
- PD-1 增强PTEN并减弱AKT/ PKC信号;PD-1 损失导致激进淋巴瘤的发展.
结论:
- 在T细胞淋巴瘤中,PD-1受体是一种强有力的瘤抑制剂.
- 人类疾病中频繁发生的PD-1变化强调了其临床意义.
- 这些发现扩大了PD-1的已知功能,并对针对T细胞淋巴瘤的免疫瘤疗法产生影响.
相关概念视频
02:23Abnormal Proliferation
5.3K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.3K
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
9.9K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.9K
01:12Loss of Tumor Suppressor Gene Functions
6.1K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
6.1K