Cell
Volume 174, Issue 5, 23 August 2018, Pages 1293-1308.e36
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Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment

https://doi.org/10.1016/j.cell.2018.05.060Get rights and content
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Highlights

  • Single-cell RNA-seq reveals phenotypic expansion of intratumoral immune cells

  • Biscuit identifies cell populations that differ in co-expression patterns

  • T cells reside on continuous activation and differentiation trajectories

  • Combinatorial environmental inputs and TCR usage shape T cell phenotypes

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.

Keywords

single-cell RNA-seq
tumor microenvironment
tumor-infiltrating immune cells
breast cancer
T cell activation
TCR utilization
Bayesian modeling

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