2. Academic Validation
  3. Modified Shenlingbaizhu decoction suppresses colon cancer via enhancing memory-like Tfh differentiation and B cell responses

Modified Shenlingbaizhu decoction suppresses colon cancer via enhancing memory-like Tfh differentiation and B cell responses

  • Phytomedicine. 2026 Apr:153:158001. doi: 10.1016/j.phymed.2026.158001.
Gurong Jiang 1,  Xinyi Yan 1,  Yeyun Zheng 1,  Linlin Zhuang 1,  Changshun Liu 2,  Jiaxuan Zhang 3,  Jinghe Liu 1,  Bojun Zhong 4,  Xuegang Sun 5
Affiliations

Affiliations

  • 1 The Key Laboratory of Molecular Biology, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China.
  • 2 Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
  • 3 Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Guangzhou 510515, China.
  • 4 Department of Traditional Chinese Medicine, Guangdong Geriatric Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
  • 5 The Key Laboratory of Molecular Biology, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China. Electronic address: [email protected].
PMID: 41763139 DOI: 10.1016/j.phymed.2026.158001
Abstract

Background: The late-stage clinical trial of immune checkpoint inhibitor (ICI) shows poor response in microsatellite stable (MSS) colorectal Cancer patients. Developing effective therapeutic strategies to enhance and prolong antitumor activity remains a significant challenge for tumor types characterized by poor T-cell infiltration.

Purpose: This study aims to explore if Modified Shenlingbaizhu Decoction (MSD) regulates anti-tumor immune response in the tumor microenvironment (TME).

Methods: The components of MSD extracts were characterized by high performance liquid chromatography (HPLC) analysis. Single-cell RNA Sequencing (scRNA-seq), flow cytometry analysis and immunofluorescence were adopted to resolve the immune landscape in MSS mice model. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration of serum IgG.

Results: MSD promoted antitumor immunity by increasing memory-like follicular helper T cells (Tfh) and B cells in mouse colon adenocarcinoma (COAD) tumors, rather than through CD8+ T cells or myeloid cells. Analysis of scRNA-seq results suggested MSD enhanced the secretion of CCL20 and CXCL13. Neutralizaion of CCL20 impaired the effects of MSD in promoting the migration of high endothelial venules (HEV)-associated B cells into tumor nests and facilitating the formation of tumor-associated aggregates (TAAs). Depletion of B cells reduced the generation of memory-like Tfh cells and impaired their stemness, thereby attenuated the therapeutic efficacy of MSD in COAD-bearing mice. During secondary immune responses, memory-like Tfh cells could rapidly transition to an effector state, promoting B cell differentiation into plasma cells and enhancing IgG antibody secretion. Mechanically, MSD upregulated Jarid2 expression in Tfh cells. Knockdown of Jarid2 in Tfh cells led to a decrease in the number of memory-like Tfh cells with stemness, and reduced the expression of the key receptor ICOS that interacted with B cells.

Conclusions: Mutual interaction between B cells and memory-like Tfh cells was promising immune response for the treatment of MSS COAD. MSD promoted the formation of TAA to intensify Tfh cell/B cell collaboration in a CCL20 dependent-manner.

Keywords

B cell response; Colon adenocarcinoma; Memory-like Tfh cells; Modified Shenlingbaizhu decoction; Tumor-associated aggregates; scRNA-seq.

Figures
Products