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

The inactivation of the APC gene is strongly associated with the initiation and progression of Colorectal Cancer (CRC). However, the specific role of Adenomatous Polyposis Coli (APC) inactivation in CRC development and its regulation of the Tumor Microenvironment (TME) remains poorly understood. In this study, we identified a distinctive feature of the APC^m+ CRC-specific TME, characterized by an enrichment of T helper 17 (Th17) cells, T follicular helper (Tfh) cells, Germinal Center (GC) B cells, and dendritic cells (DCs), by utilizing single-cell RNA (sc-RNA) sequencing data. Notably, we discovered that a key immune regulatory gene CCL20, is upregulated in APC^m+ CRC through the APC inactivation/WNT/MYC signaling pathway. The increased expression and secretion of CCL20 by APC^m+ CRC epithelial cells further facilitate the recruitment of CCR6⁺ Th17 cells to the TME, thereby promoting the shaping of the distinct APC^m+ CRC-specific TME. This work provides a comprehensive understanding of the APC^m+ specific TME, and the identified key immune regulator CCL20 may present a potential immunotherapeutic strategy for the treatment of APC^m+ CRC.