针对CCR8+调节性T细胞的免疫疗法通过对内CD8+T细胞概况的剧烈变化诱导抗瘤效应
Azumi Ueyama1,2, Wataru Nogami1, Kunitaka Nashiki1
1Laboratory for Bio-Drug Discovery, Shionogi & Co., Ltd., Toyonaka, Japan.
Journal of immunology (Baltimore, Md. : 1950)
|June 23, 2023
概括
用抗体向CCR8+调节性T细胞 (Tregs),可以逆转CD8+T细胞在瘤中的耗尽. 这种方法增强了抗瘤免疫力,促进了瘤回归,为癌症患者提供了一个有前途的策略.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 癌症研究 癌症研究
背景情况:
- 调节性T细胞 (Tregs) 创造了一个抑制瘤的微环境.
- 在瘤Tregs上选择性表达CCR8.
- 反CCR8抗体显示出消除Tregs和施加抗瘤作用的潜力.
研究的目的:
- 研究抗CCR8抗体对内免疫,特别是CD8+T细胞的作用.
- 分析CD8+T细胞激活和耗尽状态的变化.
- 在结直肠癌模型中评估向CCR8+Tregs的治疗潜力.
主要方法:
- 使用CT26结肠直肠癌小鼠模型.
- 在不同的时间点 (第5,9或12天) 服用抗CCR8抗体.
- 使用质细胞计和流细胞计进行免疫类型定型,以分析瘤透细胞,重点关注CD8+ T细胞子集和TOX表达.
主要成果:
- 抗CCR8抗体治疗增加了原始和未耗尽的效应体CD8+ T细胞,同时减少了耗尽的CD8+ T细胞 (高TOX表达).
- 延迟的抗体注射也减少了CD8+ T细胞的耗尽,并导致瘤回归.
- 高CCR8+ Treg透与人类癌症患者CD8+ T细胞中高TOX表达相关.
结论:
- 反CCR8抗体的使用有效调节CD8+T细胞的激活和衰竭,从而产生显著的抗瘤作用.
- 向CCR8+Tregs是一种有前途的治疗策略,用于具有免疫抑制微环境和CD8+T细胞耗尽的晚期癌症.
相关概念视频
Tumor Immunotherapy
575
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.
575
Cytotoxic T Cells-mediated Immune Response
998
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
998
Targeted Cancer Therapies
7.7K
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...
7.7K
The Tumor Microenvironment
6.7K
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...
6.7K


