抑制性PD-1轴保持高性干状CD8+T细胞
Jyh Liang Hor1, Edward C Schrom2, Abigail Wong-Rolle2,3
1Lymphocyte Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD, USA. jyhliang.hor@nih.gov.
Nature
|November 26, 2025
概括
检查点免疫治疗依赖于类似干细胞的毒性T细胞. 长时间的抗原接触,而不是持续的T细胞受体信号,维持这些细胞,PD-1微调它们的高亲和度扩张.
科学领域:
- 免疫学
- 癌症生物学
- T细胞生物学
背景情况:
- 干细胞类毒性T细胞对于有效的癌症免疫疗法至关重要.
- 淋巴结对产生和维持这些类似干细胞至关重要.
- 了解促进T细胞干细胞的因素是改善免疫治疗的关键.
研究的目的:
- 识别瘤排泄淋巴结中的抗原呈现,这些瘤支持类似干细胞的CD8+ T细胞.
- 阐明T细胞受体 (TCR) 信号和PD-1在维持T细胞干性的作用.
- 研究PD-1阻断对高亲和性T细胞克隆的影响.
主要方法:
- 进步的三维多重体免疫光成像.
- 在体内进行T细胞增殖和分化研究.
- 分析T细胞受体 (TCR) 信号动态和PD-1通路功能.
主要成果:
- 在瘤排水淋巴结中确定了支持干细胞T细胞扩张和亲和进化的特定位.
- 证明长时间的抗原参与, 不仅仅是初始启动, 维持干细胞T细胞的自我更新.
- 显示了PD-1通道微调TCR信号, 实现高亲和度克隆的选择性扩张.
结论:
- 长时间的抗原参与和PD-1信号传递对于保持高亲和度抗瘤T细胞的可再生池至关重要.
- PD-1 阻塞可能会破坏这一过程,导致关键的干状前体的丧失.
- 这些发现挑战了目前对T细胞分化的理解,并对优化抗PD-1癌症免疫治疗策略产生影响.
相关概念视频
T Cell Activation and Clonal Selection
14.5K
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
14.5K
Multipotency of Hematopoietic Stem Cells
3.8K
The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
3.8K
T Cell Types and Functions
2.1K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
2.1K
Abnormal Proliferation
5.0K
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...
5.0K
Cytotoxic T Cells-mediated Immune Response
6.4K
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
6.4K
Cancer Stem Cells and Tumor Maintenance
5.8K
Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
5.8K


