细胞通信网络因子4在乳腺癌中促进瘤诱导的免疫抑制
bioRxiv : the preprint server for biology
|January 16, 2026
概括
细胞通信网络因子4 (CCN4) 通过抑制抗瘤免疫力来促进乳腺癌的生长. 淘汰CCN4可以增强T细胞活性,并减少免疫抑制细胞,这表明CCN4是治疗点.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
背景情况:
- 细胞通信网络因子4 (CCN4/WISP1) 在侵袭性乳腺癌中被上调.
- 已知CCN4在黑色素瘤中促进免疫抑制.
- 有限的抗瘤免疫与乳腺癌患者的不良结果相关.
研究的目的:
- 调查CCN4与乳腺癌中瘤诱导的免疫抑制之间的直接因果关系.
- 在乳腺癌模型中评估针对CCN4的治疗潜力.
主要方法:
- 使用CCN4淘汰赛 (CCN4 KO) 的小鼠乳腺癌模型 (Py230和Py8119).
- 在免疫能力和免疫缺陷小鼠中植入了CCN4KO和野生型乳腺癌细胞.
- 分析了免疫细胞群 (T 细胞,骨髓衍生的抑制细胞) 和瘤中的脊髓巨变.
主要成果:
- 在免疫能力强但不免疫缺陷的小鼠中,CCN4KO降低了瘤生长.
- 在CCN4KO瘤中,CD4+和CD8+T细胞增加.
- 观察到骨髓体区间从多态核细胞转变为单细胞骨髓体衍生抑制细胞 (MDSC),从而减少脊髓巨变.
结论:
- 在乳腺癌中,CCN4积极促进瘤诱导的免疫抑制.
- 向CCN4可能会增强抗瘤免疫力,改善患者的治疗结果.
- CCN4是与免疫疗法结合治疗的潜在治疗标.
相关概念视频
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
Tumor Immunotherapy
1.8K
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.
1.8K
Receptor Downregulation in MVBs
2.8K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.8K
Cancer-Critical Genes II: Tumor Suppressor Genes
9.4K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.4K
Mitogens and the Cell Cycle
7.7K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.7K
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


