衰老的人类纤维细胞增加了FasL的表达,并损害了瘤的免疫反应
Monica Cruz-Barrera1,2, Joshua Dulong1,2, Georgio Mansour Nehmo1,2
1Centre de Recherche du Centre Hospitalier Universitaire (CHU) Sainte-Justine, Montréal, QC, Canada.
Frontiers in immunology
|November 12, 2025
概括
衰老性纤维细胞通过招募免疫细胞影响瘤微环境,但也通过Fas连接体 (FasL) 导致T和NK细胞死亡. 阻断FasL在人性化模型中增强了瘤细胞的杀死.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 细胞衰老影响瘤免疫力,影响免疫细胞招募和微环境免疫抑制.
- 在人性化的瘤模型中衰老的作用在很大程度上仍然没有被描述.
研究的目的:
- 在人性化的环境中研究细胞衰老对瘤免疫反应的影响.
- 阐明衰老细胞在瘤微环境中调节免疫细胞行为的机制.
主要方法:
- 利用共同培养模型,瘤球体和携带瘤的人性化小鼠.
- 在衰老的纤维细胞-瘤微环境相互作用中分析了免疫细胞的招募,细胞亡和基因表达.
主要成果:
- 衰老纤维细胞表现出双重作用,增强免疫细胞透,同时诱导T和NK细胞亡.
- 在衰老的纤维细胞上增加Fas联结体 (FasL) 表达被确定为免疫细胞亡的主要驱动因素.
- 纤维细胞特异性FasL删除可以防止免疫细胞死亡,并改善瘤细胞在体内死亡.
结论:
- FasL表达是衰老瘤微环境的关键组成部分.
- 在人性化模型中评估治疗诱导的衰老对于预测癌症治疗结果至关重要.
相关概念视频
Introduction to Fibroblasts
3.8K
Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
3.8K
Replicative Cell Senescence
4.3K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
4.3K
Abnormal Proliferation
5.1K
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...
5.1K
The Tumor Microenvironment
7.6K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
7.6K


