抗瘤CD4+T助手1细胞准并控制扩散癌细胞的外生长
Ganesan Ramamoorthi1, Marie Catherine Lee2, Carly M Farrell2
1Clinical Science & Immunology Program, Moffitt Cancer Center, Tampa, Florida.
Cancer immunology research
|April 18, 2025
概括
在瘤中激活CD4+ T辅助1 (Th1) 细胞,可以消除骨髓中扩散的癌细胞 (DCC),并防止乳腺癌转移,独立于CD8+ T细胞.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
背景情况:
- 骨髓中散布的癌细胞 (DCC) 可以预测乳腺癌的复发和转移.
- 传统疗法在消除DCC方面往往是无效的.
研究的目的:
- 为了研究抗瘤CD4+ T辅助1 (Th1) 细胞在消除DCC和预防转移方面进行内原始化的疗效.
- 阐明CD4+Th1细胞发挥抗瘤作用的机制.
主要方法:
- 在临床前乳腺癌模型中,对CD4+Th1细胞进行内原始化.
- 对T细胞迁移,表型和功能在初级瘤,淋巴结和转移部位的分析.
- 在淘汰赛小鼠模型 (CD4或IFN-γ缺乏) 中评估DCC负担和转移.
- 评估CD4+Th1细胞对DCC分子特征的影响,包括干性和MHC表达.
主要成果:
- 内CD4+ Th1细胞原始化消除了远处器官中的DCC,并防止了独立于CD8+ T细胞的转移.
- 激活的CD4+Th1细胞 (主要是CD4+PD1-) 有效地迁移到BM和转移部位.
- 在原发性瘤和转移性部位观察到记忆和效应性CD4+T细胞的增强透.
- CD4+Th1细胞对于根除DCC驱动的转移至关重要,正如淘汰赛小鼠模型所示.
- CD4+ Th1细胞增加了IFN-γ的产生,抑制了DCC分子通路,并通过调节MHC表达来增强免疫识别,从而减少DCC干和自我更新.
结论:
- 抗瘤CD4+Th1细胞的瘤内原始化是消除扩散癌细胞和预防乳腺癌复发和转移的有希望的策略.
- CD4+Th1细胞通过增强的免疫识别和减少的干细胞调节DCC瘤发生,提供一种新的基于免疫的治疗方法.
相关概念视频
01:27Tumor Immunotherapy
398
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.
398
01:27Cytotoxic T Cells-mediated Immune Response
725
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...
725
01:24T Cell Types and Functions
617
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
617
02:40Cancer 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
02:18Cancer
47.1K
Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.
47.1K
02:17The Tumor Microenvironment
6.4K
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...
6.4K