Estimating the Population Abundance of Tissue-Infiltrating Immune and Stromal Cell Populations Using Gene Expression

Genome Biol. 2016 Oct 20;17(1):218. doi: 10.1186/s13059-016-1070-5.

Abstract

We introduce the Microenvironment Cell Populations-counter (MCP-counter) method, which allows the robust quantification of the absolute abundance of eight immune and two stromal cell populations in heterogeneous tissues from transcriptomic data. We present in vitro mRNA mixture and ex vivo immunohistochemical data that quantitatively support the validity of our method's estimates. Additionally, we demonstrate that MCP-counter overcomes several limitations or weaknesses of previously proposed computational approaches. MCP-counter is applied to draw a global picture of immune infiltrates across human healthy tissues and non-hematopoietic human tumors and recapitulates microenvironment-based patient stratifications associated with overall survival in lung adenocarcinoma and colorectal and breast cancer.

Keywords: Deconvolution; Gene signatures; Transcriptomic markers; Tumor microenvironment.

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Biomarkers, Tumor
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Cell Tracking / methods*
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / pathology
  • Computational Biology*
  • Female
  • Gene Expression Profiling
  • Humans
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • RNA, Messenger / biosynthesis
  • Stromal Cells / immunology
  • Stromal Cells / pathology*
  • Transcriptome / genetics
  • Tumor Microenvironment / genetics*
  • Tumor Microenvironment / immunology

Substances

  • Biomarkers, Tumor
  • RNA, Messenger