单细胞追踪揭示黑色素瘤 TIL 治疗过程中肿瘤反应性 T 细胞的可塑性
Single-cell tracking reveals tumor-reactive T cell plasticity during melanoma TIL therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
T 细胞中免疫检查点受体信号传导
英文原题：Immune Checkpoint Receptors Signaling in T Cells.
查看英文原题
Immune Checkpoint Receptors Signaling in T Cells.
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中文摘要
负向调节淋巴细胞功能的受体的特征研究正在迅速发展，这得益于肿瘤免疫治疗的成功。因此，从功能角度被表征并被创新药物靶向的免疫检查点受体数量持续扩大。本综述聚焦于这些受体中研究较少的领域，即T细胞中表达的受体的信号传导机制。主要针对PD-1、CTLA-4和BTLA的研究表明，某些受体的胞外部分充当激活配体的诱饵受体，但在所有情况下，其胞质尾部的酪氨酸磷酸化驱动关键的抑制信号。这种负向信号由少数关键信号转导分子介导，如酪氨酸磷酸酶、肌醇磷酸酶和二酰甘油激酶，使它们能够对抗TCR介导的激活。这些信号通路的表征对于开发独立于所涉及受体、对抗TIL（肿瘤浸润淋巴细胞）耗竭/无反应性的疗法具有重大意义。
展开英文摘要原文
The characterization of the receptors negatively modulating lymphocyte function is rapidly advancing, driven by success in tumor immunotherapy. As a result, the number of immune checkpoint receptors characterized from a functional perspective and targeted by innovative drugs continues to expand. This review focuses on the less explored area of the signaling mechanisms of these receptors, of those expressed in T cells.
Studies conducted mainly on PD-1, CTLA-4, and BTLA have evidenced that the extracellular parts of some of the receptors act as decoy receptors for activating ligands, but in all instances, the tyrosine phosphorylation of their cytoplasmatic tail drives a crucial inhibitory signal.
This negative signal is mediated by a few key signal transducers, such as tyrosine phosphatase, inositol phosphatase, and diacylglycerol kinase, which allows them to counteract TCR-mediated activation. The characterization of these signaling pathways is of great interest in the development of therapies for counteracting tumor-infiltrating lymphocyte exhaustion/anergy independently from the receptors involved.
论文信息
- 作者
- Baldanzi G
- 单位
- Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy.Italy
- 文献类型
- 综述
- 期刊
- International journal of molecular sciences2022 Mar 24
- 原文标识
- PubMed 35408889 · DOI 10.3390/ijms23073529
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