抑制CDK4/6可触发抗瘤免疫力
Shom Goel1,2, Molly J DeCristo3,4, April C Watt1
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
Nature
|August 17, 2017
概括
选择性CDK4/ 6抑制剂不仅可以阻止瘤细胞循环,还可以通过增加免疫性和增强T细胞反应来增强抗瘤免疫力. 这表明癌症治疗的新组合疗法.
科学领域:
- 癌症学
- 免疫学
- 分子生物学
背景情况:
- 循环蛋白依赖性激酶4和6 (CDK4/6) 是关键的细胞循环调节剂,与各种癌症有关.
- 通过诱导细胞循环停止,CDK4/ 6 抑制剂已成为几种固体瘤的治疗方法.
研究的目的:
- 研究选择性CDK4/ 6抑制剂对抗瘤免疫力的影响.
- 阐明 CDK4/ 6 抑制剂介导的免疫增强的机制.
- 探索将CDK4/ 6抑制剂与免疫治疗结合在一起的可能性.
主要方法:
- 使用乳腺癌和其他固体瘤的小鼠模型.
- 在乳腺癌临床试验中对连续活检进行了转录基因分析.
- 研究了对瘤细胞,调节性T细胞和免疫反应的影响.
主要成果:
- CDK4/ 6 抑制剂诱导瘤细胞循环停止并促进抗瘤免疫力.
- 抑制剂激活内源性逆转录病毒元素,增加III型干扰素并增强抗原呈现.
- CDK4/ 6 抑制剂抑制了调节性T细胞的增殖,由减少的DNA甲基转移酶1活性介导.
- 这些效应促进细胞毒性T细胞清除,通过免疫检查点阻塞进一步增强.
结论:
- CDK4/ 6 抑制剂增加了瘤的免疫性.
- 这些发现支持CDK4/ 6抑制剂和免疫疗法的新组合疗法,以加强抗癌治疗.
相关概念视频
Inhibition of Cdk Activity
6.1K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.1K
Tumor Immunotherapy
2.1K
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
2.1K
M-Cdk Drives Transition Into Mitosis
6.7K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
6.7K
Abnormal 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
Positive Regulator Molecules
7.0K
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
7.0K
Targeted Cancer Therapies
9.0K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
9.0K


