糖化驱动的程序协调了骨髓系衍生抑制细胞的免疫调节和益血管功能
Ada G Blidner1, Camila A Bach1, Pablo A García2
1Laboratorio de Glicomedicina, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), 1428 Ciudad de Buenos Aires, Argentina.
Immunity
|May 17, 2025
概括
加列-1 (GAL1) 通过重编程髓质衍生抑制细胞 (MDSCs) 来抑制免疫力和促进血管生长来驱动瘤生长. 准GAL1-糖甘相互作用可能会增强癌症疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 葡萄糖生物学 葡萄糖生物学
背景情况:
- 骨髓原抑制细胞 (MDSCs) 是瘤进展的关键调节者,促进免疫抑制和血管生成.
- 连接MDSC介导的免疫抑制和亲血管功能的精确分子机制尚未完全理解.
研究的目的:
- 阐明加勒-1 (GAL1) 在调解癌症中MDSCs的双重功能中的作用.
- 研究GAL1影响MDSC表型和功能的糖化依赖机制.
主要方法:
- 对人类癌症和瘤携带小鼠的MDSC中GAL1表达的分析.
- 研究GAL1与MDSC表面受体的结合,包括CD18-CD11b-CD177复合体.
- 评估由GAL1调制的STAT3信号通路.
- 在体内使用骨髓细胞特异性基因删除和GAL1中和抗体的功能研究.
主要成果:
- GAL1表达与增强的MDSC表型和癌症预后不佳相关.
- GAL1利用利基特定的甘氨酸签名来结合MDSCs,从而激活CD18-CD11b-CD177受体综合体.
- 通过STAT3信号传递,GAL1同时通过STAT3信号在MDSC中激活免疫抑制和亲血管生成程序,驱动瘤生长.
- 干扰特定的甘氨基化途径可增强 GAL1 驱动的瘤进展, GAL1 中和可逆转.
结论:
- GAL1调节一种依赖于糖化酶的程序,使MDSC具有免疫抑制和亲血管生成能力.
- 准GAL1-甘氨酸相互作用为重新编程MDSC和改善癌症免疫疗法和抗血管生成疗法提供了潜在的治疗策略.
相关概念视频
Regulation of Hematopoietic Stem Cells
3.2K
All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
3.2K
Differentiation of Common Myeloid Progenitor Cells
3.2K
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
3.2K
Abnormal Proliferation
4.5K
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...
4.5K
T Cell Types and Functions
963
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...
963


