Single-cell analyses reveal suppressive tumor microenvironment of human colorectal cancer

Clin Transl Med. 2021 Jun;11(6):e422. doi: 10.1002/ctm2.422.

Abstract

Profiling heterologous cell types within tumors is essential to decipher tumor microenvironment that shapes tumor progress and determines the outcome of therapeutic response. Here, we comprehensively characterized transcriptomes of 34,037 single cells obtained from 12 treatment-naïve patients with colorectal cancer. Our comprehensive evaluation revealed attenuated B-cell antigen presentation, distinct regulatory T-cell clusters with different origin and novel polyfunctional tumor associated macrophages associated with CRC. Moreover, we identified expanded XCL1+ T-cell clusters associated with tumor mutational burden high status. We further explored the underlying molecular mechanisms by profiling epigenetic landscape and inferring transcription factor motifs using single-cell ATAC-seq. Our dataset and analysis approaches herein provide a rich resource for further study of the impact of immune cells and translational research for human colorectal cancer.

Keywords: human colorectal cancer; scATAC-seq; scRNA-seq; tumor immune microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / pathology
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Sequence Analysis, RNA
  • Single-Cell Analysis / methods*
  • Transcriptome*
  • Tumor Microenvironment / immunology*

Substances

  • Biomarkers, Tumor