Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment

Cell. 2018 Aug 23;174(5):1293-1308.e36. doi: 10.1016/j.cell.2018.05.060. Epub 2018 Jun 28.


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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bayes Theorem
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / pathology
  • Cluster Analysis
  • Computational Biology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immune System
  • Immunotherapy / methods
  • Lymph Nodes
  • Lymphocytes, Tumor-Infiltrating
  • Macrophages / metabolism
  • Phenotype
  • Receptors, Antigen, T-Cell / metabolism*
  • Sequence Analysis, RNA*
  • Single-Cell Analysis*
  • Transcriptome
  • Tumor Microenvironment / immunology*


  • Receptors, Antigen, T-Cell