Single-cell map of diverse immune phenotypes in the breast tumor microenvironment Journal Article

Authors: Azizi, E.; Carr, A. J.; Plitas, G.; Cornish, A. E.; Konopacki, C.; Prabhakaran, S.; Nainys, J.; Wu, K.; Kiseliovas, V.; Setty, M.; Choi, K.; Fromme, R. M.; Dao, P.; McKenney, P. T.; Wasti, R. C.; Kadaveru, K.; Mazutis, L.; Rudensky, A. Y.; Pe'er, D.
Article Title: Single-cell map of diverse immune phenotypes in the breast tumor microenvironment
Abstract: 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. Single-cell analysis of the breast tumor immune microenvironment, coupled with computational analysis, yields an immune map of breast cancer that points to continuous T cell activation and differentiation states. © 2018 Elsevier Inc.
Keywords: breast cancer; tumor microenvironment; t cell activation; bayesian modeling; single-cell rna-seq; tcr utilization; tumor-infiltrating immune cells
Journal Title: Cell
Volume: 174
Issue: 5
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2018-08-23
Start Page: 1293
End Page: 1308.e36
Language: English
DOI: 10.1016/j.cell.2018.05.060
PUBMED: 29961579
PROVIDER: scopus
Notes: Article -- Export Date: 3 December 2018 -- Source: Scopus
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