Wumei Wan remodels the tumor immune microenvironment via the Ido1-KYN-AHR axis in AOM/DSS-induced colorectal cancer model

Abstract

Background: Colorectal cancer(CRC) is a prevalent malignancy of the digestive tract, with poor prognosis in advanced stages due to metastasis and immune evasion. Chronic intestinal inflammation is increasingly recognized as a key driver of CRC progression by disrupting the immune microenvironment.Wumei Wan(WMW),a traditional Chinese herbal formula,has shown anti-inflammatory efficacy in ulcerative colitis,but its potential to inhibit CRC and modulate the immune microenvironment remains unclear.

Aim: This study aims to determine whether WMW can ameliorate CRC progression and to investigate the underlying mechanisms involved.

Methods: An azoxymethane/dextran sulfate sodium(AOM/DSS)-induced CRC mouse model was established. Integrated transcriptomics, metabolomics,and network pharmacology analyses were employed to elucidate and validate the mechanisms of WMW.

Results: WMW significantly suppressed CRC progression in mice,as demonstrated by improved colonic histology, lower Disease Activity Index(DAI) scores, increased survival rate,and reduced tumor burden.Mechanism analysis showed that WMW inhibited the IDO1-KYN-AHR pathway, reduced Th17 and Treg cell proliferation and differentiation, restored CD8⁺T cell function,and enhanced antitumor immunity.

Conclusion: This study demonstrates that WMW may suppress CRC progression by inhibiting the IDO1-KYN-AHR signaling pathway, reducing Th17 and Treg cell activity,and enhancing antitumor immune responses.Further studies are required to confirm the causal relationship of the IDO1-KYN-AHR axis in CRC progression.

Keywords: Colorectal cancer; IDO1-Kyn-AHR pathway; Network pharmacology; Transcriptomics; Wumei wan.