Systematic investigation of mitochondrial transfer between cancer cells and T cells at single-cell resolution
Systematic investigation of mitochondrial transfer between cancer cells and T cells at single-cell resolution
复制标题
DOI：
10.1016/j.ccell.2023.09.003
复制
发表时间：
2023-10-09
期刊：
影响因子：
50.3
通讯作者：
Zhang，Anli
中科院分区：
文献类型：
--
作者：
Zhang，Hongyi;Yu，Xuexin;Zhang，Anli
线粒体(MT)参与哺乳动物细胞的大部分代谢活动。最近观察到一种从T细胞到癌细胞的近单向线粒体转移，在代谢上增强了癌细胞的能力，同时“消耗了免疫细胞”，为研究肿瘤与T细胞的相互作用和免疫逃避提供了新的见解。在这里，我们利用单细胞RNA-SEQ技术并引入MERCI，这是一种统计去卷积方法，用于跟踪和量化癌症和T细胞之间的线粒体运输。通过严格的基准测试和验证，MERCI可以准确预测受体细胞及其相对线粒体组成。将MERCI应用于人类癌症样本，鉴定出一种可复制的MT转移表型，其标志性基因涉及细胞骨架重塑、能量产生和肿瘤坏死因子-α信号通路。此外，MT转移与细胞周期活性增加和不同类型癌症的不良临床结局有关。总而言之，MERCI能够系统地研究肿瘤-T细胞相互作用的一个未被研究的方面，这可能导致治疗机会的发展。
Mitochondria (MT) participate in most metabolic activities of mammalian cells. A near-unidirectional mitochondrial transfer from T cells to cancer cells was recently observed to "metabolically empower" cancer cells while "depleting immune cells," providing new insights into tumor-T cell interaction and immune evasion. Here, we leverage single-cell RNA-seq technology and introduce MERCI, a statistical deconvolution method for tracing and quantifying mitochondrial trafficking between cancer and T cells. Through rigorous benchmarking and validation, MERCI accurately predicts the recipient cells and their relative mitochondrial compositions. Application of MERCI to human cancer samples identifies a reproducible MT transfer phenotype, with its signature genes involved in cytoskeleton remodeling, energy production, and TNF-α signaling pathways. Moreover, MT transfer is associated with increased cell cycle activity and poor clinical outcome across different cancer types. In summary, MERCI enables systematic investigation of an understudied aspect of tumor-T cell interactions that may lead to the development of therapeutic opportunities.