纳米免疫调节器放大了与瘤相关的巨细胞中的STING激活,用于癌症免疫治疗
Shuang Liang1, Haiyan Ma2, Yue Liu3
1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
概括
这项研究开发了一种纳米粒子 (FANP),可以将免疫抑制M2巨细胞转化为抗瘤M1巨细胞. 这增强了抗原呈现和T细胞反应,导致了有效的癌症免疫疗法和瘤回归.
科学领域:
- 免疫学 免疫学 免疫学
- 纳米技术 纳米技术
- 癌症研究 癌症研究
背景情况:
- 瘤特异性T细胞反应依赖于抗原呈现细胞 (APC).
- 类似M2的巨细胞,在瘤中占主导地位的APC,通过不良的抗原交叉呈现损害T细胞激活.
- 恢复APC功能对于有效的癌症免疫疗法至关重要.
研究的目的:
- 设计一个纳米免疫调节器 (FANP) 来恢复M2类巨抗原呈现.
- 为了放大干扰素基因 (STING) 激活的刺激器,以增强T细胞反应.
- 调查FANP在促进抗瘤免疫力的有效性.
主要方法:
- 通过自组装Fe3+和Raddeanin A (RA) 来制造FANP.
- 在瘤微环境中的FANP降解释放Fe3+和RA.
- 评估巨细胞两极分化,STING激活,抗原交叉呈现和抗瘤反应.
主要成果:
- FANPs诱导了M2类似于M1的巨细胞两极分化.
- FANPs显著放大了STING激活的作用.
- 观察到强大的抗原交叉呈现和T细胞驱动的抗瘤反应,导致各种模型中的瘤回归.
- 在人类瘤样本中,FANPs显示了STING激活.
结论:
- 通过增加STING激活,FANPs有效地重新教育M2类巨细胞.
- 这一策略增强了T细胞介导的抗瘤免疫力.
- 在癌症免疫疗法中,FANPs具有显著的临床转化潜力.
相关概念视频
02:17The Tumor Microenvironment
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...
01:27Tumor Immunotherapy
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.