在癌症免疫疗法期间,工程热诱导性巨细胞的抗炎两极化重新编程瘤免疫微环境
Yanan Xue1,2, Xiaojie Yan2,3, Da Li1
1Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China.
Nature communications
|March 16, 2024
概括
工程化巨细胞 (eMacs) 通过切换到类似M1的表型来克服瘤微环境的挑战. 一个可穿戴的加热设备可以控制M1极化,以增强采用细胞疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 生物技术是生物技术.
- 癌症研究 癌症研究
背景情况:
- 基于巨细胞的采用细胞疗法面临着由于免疫抑制瘤微环境 (TME) 的挑战.
- 替代激活 (M2型) 巨细胞对经典激活 (M1型) 现型的偏差限制了治疗疗效.
- 瘤相关巨细胞 (TAMs) 在TME中经常表现出一种免疫抑制的M2类表型.
研究的目的:
- 开发一种工程化巨细胞 (eMac) 系统,以克服采用细胞治疗中的偏振缺陷.
- 调查eMac在TME中自我极化和再极化TAM的能力.
- 建立一种安全可控的方法来增强M1巨细胞分极 in vivo.
主要方法:
- 开发了带有可热诱导基因开关的eMac,用于控制极化.
- 使用鼠标模型在TME中评估eMac的性能.
- 使用可穿戴加热设备进行局部温度升高和远程控制.
主要成果:
- 工程化巨细胞 (eMacs) 在轻微的温度升高后成功地极化为类似M1的表型.
- 通过采用转移的eMac显示了自我极化,TAM被重新极化为类似M1的表型.
- 通过eMacs产生的局部细胞因子产生诱导了M1极化,没有系统性副作用.
- 一个智能手机控制的可穿戴加热设备被开发用于潜在的人类应用.
结论:
- 带有热诱导开关的工程巨细胞为增强基于巨细胞的采用细胞治疗提供了一个有希望的策略.
- 通过局部变暖控制的M1极化提供了一种安全有效的方法来重新编程TME.
- 这项技术有可能转化为人类癌症免疫治疗.
相关概念视频
02:17The Tumor Microenvironment
6.6K
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...
6.6K
01:27Tumor Immunotherapy
524
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.
524
01:28Inflammatory Response
2.0K
An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
2.0K