T细胞受体
CD8型
T细胞
生物
癌症研究
细胞
核糖核酸
细胞毒性T细胞
基因
计算生物学
分子生物学
免疫系统
免疫学
抗原
遗传学
体外
作者
Dev Bhatt,Boxi Kang,Deepali V. Sawant,Liangtao Zheng,Kristy C. Perez,Zhiyu Huang,Laura Sekirov,Daniel J. Wolak,Julie Y. Huang,Xian Liu,Jason DeVoss,Paolo Manzanillo,Nathan E. Pierce,Zemin Zhang,Antony Symons,Wenjun Ouyang
摘要
Single-cell RNA sequencing is a powerful tool to examine cellular heterogeneity, novel markers and target genes, and therapeutic mechanisms in human cancers and animal models. Here, we analyzed single-cell RNA sequencing data of T cells obtained from multiple mouse tumor models by PCA-based subclustering coupled with TCR tracking using the STARTRAC algorithm. This approach revealed various differentiated T cell subsets and activation states, and a correspondence of T cell subsets between human and mouse tumors. STARTRAC analyses demonstrated peripheral T cell subsets that were developmentally connected with tumor-infiltrating CD8+ cells, CD4+ Th1 cells, and T reg cells. In addition, large amounts of paired TCRα/β sequences enabled us to identify a specific enrichment of paired public TCR clones in tumor. Finally, we identified CCR8 as a tumor-associated T reg cell marker that could preferentially deplete tumor-associated T reg cells. We showed that CCR8-depleting antibody treatment provided therapeutic benefit in CT26 tumors and synergized with anti-PD-1 treatment in MC38 and B16F10 tumor models.
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