可诱导的CCR2+非经典单细胞介导癌症转移的回归
Xianpeng Liu1, Ziyou Ren2, Can Tan3
1Division of Thoracic Surgery/Canning Thoracic Institute, Feinberg School of Medicine, Northwestern University/Northwestern Medicine, Chicago, Illinois, USA.
The Journal of clinical investigation
|November 15, 2024
概括
通过诱导特定的单细胞,可以克服癌症免疫疗法耐药性. 在古典单细胞中激活NOD2会产生CCR2+非古典单细胞,这些单细胞透到瘤中,招募NK细胞,并促进癌症回归.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 移动通信贩运 移动通信贩运
背景情况:
- 免疫疗法耐药性是癌症治疗的一个主要挑战,通常是由癌症诱导的免疫反应抑制所驱动的.
- 癌细胞利用CCL2 (化学C-C动因联接体2) 来招募表达CCR2 (C-C化学受体类型2) 的经典单细胞,促进转移和免疫逃避.
- 表达CR2的古典单细胞可以分化为具有抗癌特性的血管内非古典单细胞,但它们很难到达瘤部位.
研究的目的:
- 研究一种独特的CCR2表达非古典单细胞子集及其在克服免疫疗法耐药性的潜在治疗作用.
- 探索扩大和诱导这些单细胞以增强抗癌活性的方法.
主要方法:
- 在炎症条件下 (器官移植,COVID-19) 分析小鼠和人类中表达CCR2的非经典单细胞群.
- 在实验室中使用NOD2 (核酸结合寡合化域含蛋白2) 激活剂对古典单细胞诱导这些单细胞.
- 在黑色素瘤,肺癌,乳腺癌和结肠癌的小鼠模型中评估可诱导的CCR2+非经典单细胞透和抗瘤疗效.
主要成果:
- 不太代表的CCR2+非经典单细胞的一个子集在炎症期间被扩大,并且可以通过NOD2激活来诱导.
- 这些可诱导的CCR2+非古典单细胞有效地透了小鼠的各种瘤类型,逆转了Nod2-/-小鼠的转移.
- 在瘤中,这些单细胞分泌CCL6 (化学C-C动因联接体6) 来招募NK细胞,导致瘤回归,独立于T和B细胞.
结论:
- 对CCR2+非经典单细胞的药理诱导是治疗耐免疫治疗癌症的一个有前途的策略.
- 这种方法利用先天性免疫细胞 (NK细胞) 进行瘤回归,为淋巴细胞依赖机制提供了替代方案.
更多相关视频
相关概念视频
Metastasis
5.5K
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
5.5K
Cancer Cell Migration through Invadopodia
2.3K
Invadosome is a broad category of cell surface structures with proteolytic activity that degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
2.3K
Non-Canonical Wnt Signaling Pathways
7.2K
Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
7.2K
Chemotaxis and Direction of Cell Migration
3.3K
Cells can detect chemical cues in their environment and reorganize the cytoskeleton to migrate toward them or away from them. This directional migration, called chemotaxis, is essential during embryogenesis and development, immune response, tissue repair and regeneration, and reproduction. These chemical cues can either attract or repel the cell's movement. For example, axon development is determined by a combination of chemoattractants and chemorepellents that direct the growing axon...
3.3K
Cancer Stem Cells and Tumor Maintenance
4.9K
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...
4.9K
The 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


