针对腺素介导的代谢性免疫检查点,使用工程益生菌进行增强化疗免疫疗法
Jinhui Wang1, Jing Wang1, Zhijie Yu2
1MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, IGCME, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510006, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|February 22, 2025
概括
工程细菌将瘤中的免疫抑制性腺素转化为因素,增强抗瘤免疫力. 这种益生菌策略重塑瘤微环境 (TME),以改善癌症免疫治疗结果.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
背景情况:
- 癌症免疫疗法的有效性受到免疫抑制性瘤微环境 (TME) 的限制.
- 在TME中积累的腺素通过cAMP信号抑制了抗瘤免疫细胞的功能.
- 向腺代谢是克服免疫抑制的潜在策略.
研究的目的:
- 开发一种基因工程益生菌,用于在TME内部的局部腺降解.
- 在结肠直肠癌模型中评估工程Escherichia coli Nissle 1917表达腺脱氨酶的疗效.
- 评估工程益生菌对TME内的免疫细胞透和表型的影响.
主要方法:
- 在低氧条件下对大肠杆菌Nissle 1917进行基因工程以表达表面腺脱氨酶.
- 将工程益生菌给皮下和直肠直肠癌小鼠模型.
- 在瘤组织中分析免疫细胞群 (巨细胞,T细胞) 和细胞因子概况.
- 对低剂量多克索鲁比化疗的协同效应的评估.
主要成果:
- 工程化益生菌成功向瘤并将腺降解为 inosine.
- 抗瘤免疫细胞透的显著增加,包括效应T细胞.
- 调节TME,其特点是从M2类转向M1类巨细胞.
- 当与低剂量多克索鲁比辛相结合时,观察到协同作用的抗瘤作用.
结论:
- 基因工程益生菌可以通过代谢腺来有效地重塑免疫抑制性TME.
- 这种方法增强了抗瘤免疫反应,并增强了化疗的疗效.
- 工程益生菌代表了改善癌症免疫治疗的有希望的新战略.
相关概念视频
01:27Tumor Immunotherapy
463
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.
463
02:57Targeted Cancer Therapies
7.4K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.4K
02:50Combination Therapies and Personalized Medicine
4.8K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
4.8K