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

  • Biochem Pharmacol. 2026 Aug;250(Pt 1):117992. doi: 10.1016/j.bcp.2026.117992.
Xianli Shi  1 ,  Haoming Chen  2 ,  Rui Li  2 ,  Ziyue Zhong  2 ,  Xiaoqing Lu  2 ,  Xueqing Kong  2 ,  Jiangchao Li  3 ,  Shanshan Wang  2 ,  Wenjing Guo  4 ,  Rongxin Zhang  5
Affiliations
  • 1. Department of Biochemistry, School of Basic Medical Science, Guangdong Pharmaceutical University, Guangzhou 510006, China; Laboratory of Oncology and Immunology, School of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China.
  • 2. Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Department of Biotechnology, Laboratory of Immunology and Inflammation, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China.
  • 3. Laboratory of Oncology and Immunology, School of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China.
  • 4. Analytical Instrumentation Core, Guangzhou Institute of Biomedicine and Health (GIBH), Chinese Academy of Sciences, 190 Kai Yuan Avenue, Science Park, Guangzhou 510530, China.
  • 5. Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Department of Biotechnology, Laboratory of Immunology and Inflammation, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China; The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China; The Second Clinical Medical School of Guangdong Pharmaceutical University, Guangzhou, China. Electronic address: [email protected].
PMID: 42002233 DOI: 10.1016/j.bcp.2026.117992
Abstract

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 APCm+ 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 APCm+ CRC through the APC inactivation/Wnt/MYC signaling pathway. The increased expression and secretion of CCL20 by APCm+ CRC epithelial cells further facilitate the recruitment of CCR6+ Th17 cells to the TME, thereby promoting the shaping of the distinct APCm+ CRC-specific TME. This work provides a comprehensive understanding of the APCm+ specific TME, and the identified key immune regulator CCL20 may present a potential immunotherapeutic strategy for the treatment of APCm+ CRC.

Keywords
CCL20; CCR6; CRC; Sc-RNA; TME.
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