Author:
Azizi Elham,Carr Ambrose J.,Plitas George,Cornish Andrew E.,Konopacki Catherine,Prabhakaran Sandhya,Nainys Juozas,Wu Kenmin,Kiseliovas Vaidotas,Setty Manu,Choi Kristy,Fromme Rachel M.,Dao Phuong,McKenney Peter T.,Wasti Ruby C.,Kadaveru Krishna,Mazutis Linas,Rudensky Alexander Y.,Pe’er Dana
Abstract
SUMMARYKnowledge of immune cell phenotypes in the tumor microenvironment is essential for understanding mechanisms of cancer progression and immunotherapy response. We created an immune map of breast cancer using single-cell RNA-seq data from 45,000 immune cells from eight breast carcinomas, as well as matched normal breast tissue, blood, and lymph node. 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 tumor-specific phenotypic expansions driven by environmental cues. 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, with important implications for characterizing tumor-infiltrating immune cells.
Publisher
Cold Spring Harbor Laboratory
Cited by
16 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献