https://doi.org/10.1016/j.apsb.2025.05.013
This new article publication from Acta Pharmaceutica Sinica B, discusses how single-cell RNA sequencing reveals that Shen-Bai-Jie-Du decoction retards colorectal tumorigenesis by regulating the TMEM131–TNF signaling pathway-mediated differentiation of immunosuppressive dendritic cells.
Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, single-cell RNA sequencing (scRNA-seq) was employed to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. The results constructed the mutually verifiable single-cell transcriptomic atlases in ApcMin/+ mice and clinical patients. There was a marked accumulation of CCL22+ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22+ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22+ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.
Keywords: Single-cell RNA sequencing, Colorectal tumorigenesis, Tumor microenvironment, Traditional Chinese medicine, CCL22+ dendritic cells, CD4+ regulatory T cells, TMEM131, TNF signaling pathway
Graphical Abstract: available at https://ars.els-cdn.com/content/image/1-s2.0-S221138352500320X-ga1_lrg.jpg
Single-cell RNA sequencing in ApcMin/+ mice and clinical specimens demonstrates that Shen-Bai-Jie-Du decoction inhibits colorectal tumorigenesis by regulating TMEM131–TNF signaling pathway-mediated differentiation of immunosuppressive dendritic cells.