Identify CCL20 as the key immune microenvironment regulator in APC-mutation colon cancer by sc-RNA data analysis

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Adenomatous Polyposis Coli (APC) gene inactivation is linked to Colorectal Cancer (CRC) initiation and progression.
• The precise role of APC inactivation in CRC development and its impact on the Tumor Microenvironment (TME) are not fully understood.

Purpose of the Study:

• To characterize the specific TME in APC-inactivated (APC^m+) CRC.
• To elucidate the molecular mechanisms regulating the APC^m+ CRC-specific TME.
• To identify potential therapeutic targets for APC^m+ CRC.

Main Methods:

• Single-cell RNA sequencing (sc-RNA) was used to analyze the TME of APC^m+ CRC.
• Analysis of the APC inactivation/WNT/MYC signaling pathway was performed.
• Immune cell populations and gene expression, specifically CCL20, were investigated.

Main Results:

• A distinct APC^m+ CRC-specific TME was identified, enriched with T helper 17 (Th17) cells, T follicular helper (Tfh) cells, Germinal Center (GC) B cells, and dendritic cells (DCs).
• CCL20, a key immune regulatory gene, was found to be upregulated in APC^m+ CRC via the APC inactivation/WNT/MYC pathway.
• Increased CCL20 expression and secretion by CRC epithelial cells recruit CCR6⁺ Th17 cells, shaping the APC^m+ TME.

Conclusions:

• This study provides a comprehensive understanding of the APC^m+ CRC-specific TME.
• The identified immune regulator, CCL20, presents a potential immunotherapeutic strategy for APC^m+ CRC treatment.