雌激素会增加癌细胞的细胞增生,从而形成一种免疫抑制性瘤微环境
bioRxiv : the preprint server for biology
|January 7, 2025
概括
激素17β-雌二醇 (E2) 增强了瘤相关巨细胞 (TAMs) 罩癌细胞,抑制了抗癌免疫力. 针对这种E2/ER/CX3CR1通路可以逆转这种抑制并改善癌症疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
- 癌症生物学 癌症生物学
背景情况:
- 与瘤相关的巨细胞 (TAMs) 通过瘤癌细胞的细胞分裂促进免疫抑制的瘤微环境.
- 类固醇激素17β-雌激醇 (E2) 通过TAMs中的雌激素受体α (ERα) 信号影响瘤免疫力.
研究的目的:
- 阐明E2增强TAM乙细胞分裂并抑制抗癌免疫力的机制.
- 研究向E2/ERα/CX3CR1轴在癌症治疗中的治疗潜力.
主要方法:
- 使用遗传学和药理学方法在TAM中研究了E2诱导的CX3CR1表达.
- 评估了E2/ERα/CX3CR1轴对乙细胞分裂,I型干扰素信号传递和T细胞激活的影响.
- 评估了在临床前癌症模型中与放射治疗结合针对这一轴的有效性.
主要成果:
- E2通过ERα和NFATC1对TAM中的CX3CR1进行升级调节,促进细胞增生并抑制I型干扰素信号传递.
- 抑制E2/ERα/CX3CR1轴逆转了TAM介导的免疫抑制,并增强了抗瘤免疫反应.
- 向ERα或CX3CR1通过恢复T细胞激活,提高了放射治疗的疗效.
结论:
- 通过通过ERα/CX3CR1通路增强TAM细胞生成,E2促进了免疫抑制性瘤微环境.
- 通过内分泌疗法向这种途径提供了一个有希望的策略,以克服瘤免疫抵抗力并提高癌症治疗效率.
相关概念视频
The 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
Mitogens and the Cell Cycle
6.3K
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...
6.3K
Tumor Immunotherapy
391
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.
391
Metastasis
5.3K
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
5.3K
Cancer Stem Cells and Tumor Maintenance
4.6K
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...
4.6K
Adaptive Mechanisms in Cancer Cells
5.5K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.5K


