生物
免疫系统
肿瘤微环境
T细胞受体
T细胞
免疫
单细胞分析
细胞
单细胞测序
表型
免疫学
免疫疗法
癌症研究
计算生物学
遗传学
基因
外显子组测序
作者
Elham Azizi,A. J. H. Carr,George Plitas,Andrew Cornish,Catherine Konopacki,Sandhya Prabhakaran,Juozas Nainys,Kenmin Wu,Vaidotas Kiseliovas,Manu Setty,Kristy Choi,Rachel M. Fromme,Phuong Dao,Peter T. McKenney,Ruby Wasti,Krishna Kadaveru,Linas Mažutis,Alexander Y. Rudensky,Dana Pe’er
出处
期刊:Cell
[Elsevier]
日期:2018-08-01
卷期号:174 (5): 1293-1308.e36
被引量:1344
标识
DOI:10.1016/j.cell.2018.05.060
摘要
Summary
Knowledge of immune cell phenotypes in the tumor microenvironment is essential for understanding mechanisms of cancer progression and immunotherapy response. We profiled 45,000 immune cells from eight breast carcinomas, as well as matched normal breast tissue, blood, and lymph nodes, using single-cell RNA-seq. We developed a preprocessing pipeline, SEQC, and a Bayesian clustering and normalization method, Biscuit, to address computational challenges inherent to single-cell data. Despite significant similarity between normal and tumor tissue-resident immune cells, we observed continuous phenotypic expansions specific to the tumor microenvironment. Analysis of paired single-cell RNA and T cell receptor (TCR) sequencing data from 27,000 additional T cells revealed the combinatorial impact of TCR utilization on phenotypic diversity. Our results support a model of continuous activation in T cells and do not comport with the macrophage polarization model in cancer. Our results have important implications for characterizing tumor-infiltrating immune cells.
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