在高度血清性卵巢癌中,PTEN损失塑造了巨细胞动力学
Sarah Spear1, Olivia Le Saux1,2, Hasan B Mirza1
1Ovarian Cancer Action Research Centre, Department of Surgery & Cancer, Imperial College London; London, United Kingdom.
Cancer research
|August 26, 2024
概括
高度血清性卵巢癌 (HGSC) 与PTEN损失的特征是促进瘤的巨细胞. 向这些巨细胞中的血红氧酶-1 (HMOX1) 可能为高血糖细胞患者提供一种新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 高度血清性卵巢癌 (HGSC) 的预后不佳,并且耐受免疫检查点抑制剂.
- 包括PTEN丧失在内的PI3K路径改变在HGSC中很常见,但治疗向一直没有成功.
- 异常的PI3K通路激活可能会影响HGSC免疫微环境,呈现出潜在的治疗脆弱性.
研究的目的:
- 调查PI3K通路激活在塑造HGSC免疫微环境中的作用.
- 为了确定与PTEN缺乏的HGSC.相关的特定巨细胞群.
- 探索向血红素酶-1 (HMOX1) 作为HGSC的治疗策略.
主要方法:
- 在Pten-null HGSC的小鼠模型中进行单细胞RNA测序和流细胞计.
- 分析瘤细胞和瘤透巨细胞中的基因表达.
- 在体内实验涉及准腹膜巨细胞和直接抑制HMOX1.
- 对巨细胞群的相关性分析与来自人类HGSC患者的临床数据.
主要成果:
- Pten-null HGSC模型表现出独特的居住腹巨细胞 (HMOX1hi巨细胞) 来自腹液巨细胞.
- 向这些巨细胞或抑制HMOX1可以减少瘤生长,并在体内延长存活时间.
- 在Pten-null瘤细胞中的IL33被确定为HMOX1hi巨征集的潜在驱动因素.
- 人类HGSC瘤显示HMOX1hi巨细胞的丰富,与激活PI3K/mTOR信号传递和生存率差相关.
结论:
- HMOX1hi巨细胞是PTEN缺乏HGSC的标志,并有助于瘤的进展.
- 向HMOX1hi巨细胞代表了改善HGSC结果的有希望的治疗途径.
- HMOX1hi巨细胞的存在与HGSC瘤的适应性免疫反应相反相关.
相关概念视频
02:23Abnormal Proliferation
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 daughter...
02:53Adaptive Mechanisms in Cancer Cells
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
01:12Loss of Tumor Suppressor Gene Functions
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...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
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...
01:20The Retinoblastoma Gene
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.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:19Cadherins in Tissue Organization
The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Cell Sorting During Development
Cell sorting plays an...