This new article publication from Acta Pharmaceutica Sinica B, discusses how single-cell RNA sequencing reveals that Shen-Bai-Jie-Du decoction retards colorectal tumourigenesis by regulating the TMEM131–TNF signalling pathway-mediated differentiation of immunosuppressive dendritic cells.

Colorectal tumourigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumour microenvironment (TME).

A randomised controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumourigenesis.

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 utilised to assess the underlying mechanisms.

The results constructed the mutually verifiable single-cell transcriptomic atlases in Apc^Min/+ 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 signalling pathway and may be a potential target of berberine in retarding colorectal tumourigenesis.

These findings emphasise 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 tumourigenesis, Tumour microenvironment, Traditional Chinese medicine, CCL22⁺ dendritic cells, CD4⁺ regulatory T cells, TMEM131, TNF signalling pathway

Graphical Abstract: available at https://ars.els-cdn.com/content/image/1-s2.0-S221138352500320X-ga1_lrg.jpg

Single-cell RNA sequencing in Apc^Min/+ mice and clinical specimens demonstrates that Shen-Bai-Jie-Du decoction inhibits colorectal tumourigenesis by regulating TMEM131–TNF signalling pathway-mediated differentiation of immunosuppressive dendritic cells.

Source: Compuscript Ltd