CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The mosquito effect: regulatory and effector T cells acquire cytoplasmic material from tumor cells through intercellular transfer.
The mosquito effect: regulatory and effector T cells acquire cytoplasmic material from tumor cells through intercellular transfer.
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细胞间转移细胞物质(包括膜、细胞质甚至细胞器)的现象已被观察了数十年。由于缺乏稳健的体内模型,这种转移在免疫系统中的功能影响和分子机制在很大程度上仍不清楚。在此,我们引入了一种新的肿瘤小鼠模型,其中肿瘤细胞表达可溶性超亮荧光蛋白ZsGreen,从而能够检测和测量细胞质从肿瘤细胞向浸润免疫细胞的细胞间转移。我们发现,除了多种类型的髓系细胞外,很大一部分T调节细胞和效应CD8 T细胞也获得了肿瘤物质。根据肿瘤来源的ZsGreen的分布,大多数T细胞将捕获的细胞质整合到自身的细胞质中,而大多数髓系细胞则将肿瘤物质储存在颗粒中。此外,scRNA-seq分析揭示,获得肿瘤细胞细胞质的T细胞的转录组发生了显著改变,提示可能对T细胞功能产生影响。我们发现T细胞参与细胞间转移需要细胞间接触,并且严格依赖于T淋巴细胞的活化状态。最后,我们建议将所描述的肿瘤浸润T细胞的细胞间转移现象命名为“蚊子效应”。
The phenomenon of intercellular transfer of cellular material, including membranes, cytoplasm, and even organelles, has been observed for decades. The functional impact and molecular mechanisms of such transfer in the immune system remain largely elusive due to the absence of a robust in vivo model.
Here, we introduce a new tumor mouse model, where tumor cells express the soluble ultra-bright fluorescent protein ZsGreen, which allows detection and measurement of intercellular transfer of cytoplasm from tumor cells to infiltrating immune cells.
We found that in addition to various types of myeloid lineage cells, a large fraction of T regulatory cells and effector CD8 T cells acquire tumor material. Based on the distribution of tumor-derived ZsGreen, the majority of T cells integrate captured cytoplasm into their own, while most myeloid cells store tumor material in granules.
Furthermore, scRNA-seq analysis revealed significant alterations in transcriptomes of T cells that acquired tumor cell cytoplasm, suggesting potential impact on T cell function.
We identified that the participation of T cells in intercellular transfer requires cell-cell contact and is strictly dependent on the activation status of T lymphocytes.
Finally, we propose to name the described phenomenon of intercellular transfer for tumor infiltrating T cells the "mosquito effect".
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