肠道微生物群诱导的CTLA4在CD8+ T细胞上的表达会损害抗瘤免疫力,并促进结肠直肠癌的进展
Meidie Cheng1, Shuangcheng Zhi1, Mengmeng Zheng1
1College of Life Science and Engineering, Henan University of Urban Construction, Pingdingshan, China.
Immunology
|March 4, 2026
概括
这项研究揭示了肠道细菌与肠直肠癌 (CRC) 中的免疫细胞联系. 肠道失生症通过CTLA4驱动CD8+T细胞耗尽,促进瘤生长,但便微生物群移植 (FMT) 显示出治疗前景.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 在瘤学瘤学.
背景情况:
- 大肠直肠癌 (CRC) 经常与免疫抑制瘤微环境有关.
- 肠道微生物群在CRC中调节抗瘤免疫力的作用仍然不完全理解.
研究的目的:
- 阐明肠道微生物群组成与结直肠癌中CD8+T细胞介导的免疫抑制之间的机制联系.
- 调查针对已识别的微生物群-CD8+T细胞轴的治疗潜力.
主要方法:
- 用于肠道微生物群分析的16S rRNA测序.
- 单细胞和空间转录组学,以描述瘤免疫细胞及其相互作用.
- 功能性测试和体内模型与便微生物群移植 (FMT) 和CTLA4敲击.
主要成果:
- 在CRC患者中观察到显著的肠道失调 (丰富的Phocaeicola和Bacteroides).
- 增加CTLA4+PD1+CD8+T细胞与瘤细胞同位,表明直接免疫抑制.
- 通过促进T细胞激活和减少免疫抑制性CD8+T细胞,FMT改善了CRC症状.
- CTLA4过度表达会损害CD8+ T细胞功能,加速CRC的进展.
结论:
- 一种新的肠道微生物群-CD8+T细胞轴,由CTLA4上调驱动,促进结直肠癌中的免疫逃避.
- 针对这一轴,可能通过FMT或CTLA4调制,为CRC免疫疗法提供了一个有前途的治疗策略.
更多相关视频
06:57Development of an Antigen-driven Colitis Model to Study Presentation of Antigens by Antigen Presenting Cells to T Cells
Published on: September 18, 2016
9.7K
07:34Induction of Intestinal Inflammation by Adoptive Transfer of CBir1 TCR Transgenic CD4+ T Cells to Immunodeficient Mice
Published on: December 16, 2021
3.3K
相关概念视频
02:17The Tumor Microenvironment
6.3K
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...
6.3K
01:27Tumor Immunotherapy
2.5K
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.
2.5K
01:18Functions of the Gut Microbiota
233
The gut microbiota includes trillions of microorganisms that colonize the human gastrointestinal tract, including bacteria, archaea, viruses, and fungi. This complex ecosystem plays a critical role in maintaining intestinal and systemic health. Most of these microbes inhabit the large intestine, establishing a relatively stable and diverse community that contributes to gut homeostasis through various metabolic, immunological, and protective mechanisms.Dominant bacterial phyla, such as...
233
01:20Inflammatory Bowel Disease II: Ulcerative Colitis
34
Ulcerative colitis is a chronic inflammatory disorder of the colon characterized by continuous mucosal inflammation that typically begins in the rectum and extends proximally in a uniform pattern. Its pathogenesis involves a complex interplay of genetic predisposition, immune dysregulation, and environmental influences. These factors converge to impair the colon’s epithelial defenses and promote an exaggerated inflammatory response against luminal contents.Breakdown of the Mucosal...
34
01:25Inflammatory Bowel Disease III: Crohn's Disease
35
Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...
35