STARTRAC analyses of scRNAseq data from tumor models reveal T cell dynamics and therapeutic targets.
STARTRAC analyses of scRNAseq data from tumor models reveal T cell dynamics and therapeutic targets.
复制标题
DOI：
10.1084/jem.20201329
复制
发表时间：
2021-06-07
期刊：
影响因子：
--
通讯作者：
Ouyang W
中科院分区：
文献类型：
--
作者：
Bhatt D;Kang B;Sawant D;Zheng L;Perez K;Huang Z;Sekirov L;Wolak D;Huang JY;Liu X;DeVoss J;Manzanillo PS;Pierce N;Zhang Z;Symons A;Ouyang W
对MC38和CT26肿瘤模型的T细胞进行单细胞RNAseq分析。基于pca的亚聚类和STARTRAC分析揭示了肿瘤中微调的T细胞亚群和动态。CCR8被确定为Tregs上与抗pd -1协同治疗癌症免疫治疗的新靶点。单细胞RNA测序是研究人类癌症和动物模型中细胞异质性、新标记物和靶基因以及治疗机制的有力工具。在这里，我们通过基于pca的亚聚类结合使用STARTRAC算法的TCR跟踪，分析了从多个小鼠肿瘤模型中获得的T细胞单细胞RNA测序数据。该方法揭示了不同分化的T细胞亚群和激活状态，以及人和小鼠肿瘤之间T细胞亚群的对应关系。STARTRAC分析显示外周T细胞亚群与肿瘤浸润性CD8+细胞、CD4+ Th1细胞和T reg细胞发育相关。此外，大量配对的TCRα/β序列使我们能够鉴定肿瘤中配对的公共TCR克隆的特异性富集。最后，我们发现CCR8是一种肿瘤相关的T regg细胞标志物，可以优先消耗肿瘤相关的T regg细胞。在MC38和B16F10肿瘤模型中，我们发现ccr8耗尽抗体治疗在CT26肿瘤中提供了治疗效果，并与抗pd -1治疗协同。
Single cell RNAseq analyses were performed on T cells from MC38 and CT26 tumor models. PCA-based sub-clustering and STARTRAC analyses revealed fine-tuned T cell subsets and dynamic in tumor. CCR8 was identified as a novel target on Tregs to synergize with anti–PD-1 for cancer immunotherapy. 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.
登录
查看更多内容
影响因子：
30.5
作者：
Galletti G;De Simone G;Mazza EMC;Puccio S;Mezzanotte C;Bi TM;Davydov AN;Metsger M;Scamardella E;Alvisi G;De Paoli F;Zanon V;Scarpa A;Camisa B;Colombo FS;Anselmo A;Peano C;Polletti S;Mavilio D;Gattinoni L;Boi SK;Youngblood BA;Jones RE;Baird DM;Gostick E;Llewellyn-Lacey S;Ladell K;Price DA;Chudakov DM;Newell EW;Casucci M;Lugli E
通讯作者：
Lugli E
DOI：
10.1073/pnas.0807954105
发表时间：
2008-09-30
影响因子：
11.1
作者：
Derre, Laurent;Bruyninx, Marc;Rufer, Nathalie
通讯作者：
Rufer, Nathalie
影响因子：
7.3
作者：
Garner LC;Klenerman P;Provine NM
通讯作者：
Provine NM
DOI：
10.1084/jem.20180684
发表时间：
2018-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Brummelman J;Mazza EMC;Alvisi G;Colombo FS;Grilli A;Mikulak J;Mavilio D;Alloisio M;Ferrari F;Lopci E;Novellis P;Veronesi G;Lugli E
通讯作者：
Lugli E
DOI：
10.1073/pnas.1621280114
发表时间：
2017-06-06
影响因子：
11.1
作者：
Barsheshet, Yiftah;Wildbaum, Gizi;Karin, Nathan
通讯作者：
Karin, Nathan