Single-Cell Profiling Reveals Distinct Immune Hallmarks in Untreated Primary Colorectal and Liver Metastasis Cancers

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Colorectal cancer (CRC) is a globally prevalent cancer with a poor prognosis for metastatic disease.
• The high metastasis rate in CRC, particularly to the liver, results in a 5-year survival rate of only 10%.
• Understanding the tumor microenvironment (TME) at primary and metastatic sites is critical for deciphering CRC progression.

Purpose of the Study:

• To decode the TME differences between primary colorectal cancer and liver metastasis.
• To identify novel cellular and molecular characteristics of the metastatic TME.
• To explore potential therapeutic targets and biomarkers for metastatic CRC.

Main Methods:

• Single-cell sequencing and analysis of 36 samples from four anatomical locations in nine untreated CRC liver metastasis patients.
• Comparison of cell types and gene expression between primary and metastatic sites.
• Validation of TME features and statistical analysis using nonparametric tests.

Main Results:

• Identification of eleven major cell types with significant heterogeneity in distribution across primary and metastatic sites.
• Discovery of enriched CXCL13+ CD4 T cells, regulatory CD4 T cells, increased exhausted CD8+ T cells (Tex), SPP1+ tumor macrophages, and IGFBP7+ cancer-associated fibroblasts in liver metastases.
• Observation of activated linoleic acid metabolism and four distinct biological modules (apoptosis, epithelial-mesenchymal transition, cell cycle, immune processes) in tumor cells.

Conclusions:

• The study provides novel insights into the unique features of the TME in colorectal cancer liver metastasis.
• Identified TME characteristics may serve as potential biomarkers for early detection and prognosis.
• Findings suggest new avenues for developing targeted treatment strategies against metastatic CRC.