ShenqiYichang decoction enhances colorectal cancer immune efficacy via IDO1 mediated reduction of Treg infiltration.

Authors

Yunhe Yang, Lingchang Li, Yuxi Fang, Zhou Yang, Rongtao Xue, Meng Gao, Lamei Zhou, Jian Zhang, Dongjian Zhang

Published in

Journal of ethnopharmacology. Pages 122432. Oct 13, 2026. Epub Oct 13, 2026.

Abstract

ShenqiYichang decoction (SQYCD) is a traditional Chinese formula indicated for colorectal cancer (CRC). Studies have shown that SQYCD potentiates antitumor immunity and enhances the efficacy of immune checkpoint inhibitors (ICIs).
This study aimed to investigate the mechanism of SQYCD in enhancing ICIs efficacy against microsatellite stability (MSS) CRC.
An in vivo CT26 tumor-bearing mouse model was established. The antitumor efficacy of SQYCD alone and in combination with ICIs was evaluated, and Treg infiltration was detected by immunofluorescence. Network pharmacology and bioinformatics were used to screen potential targets of SQYCD for MSS CRC. In vitro, MSS CRC cell lines were used for CCK-8 to assess cell proliferation. A CT26-Treg co-culture system was used to analyze Treg proportion by flow cytometry. Western blot, qRT-PCR, ELISA, and Co-IP assays were used to assess the IDO1/Kyn/p-AKT axis and IDO1-PI3K interactions. UPLC-Q-TOF/MS and molecular docking were subsequently employed to identify the key absorbed components involved in the IDO1-PI3K pathway regulated by SQYCD.
In vivo, SQYCD alone did not affect the proliferation of MSS CRC cells but inhibited Treg infiltration. When combined with ICIs, SQYCD enhanced the efficacy of ICIs, significantly inhibiting tumor cell proliferation and further reducing Treg infiltration. Network pharmacology and bioinformatics analysis suggested IDO1 as a potential target of SQYCD in MSS CRC. In vitro, SQYCD-containing serum did not reduce MSS CRC cell proliferation but decreased Treg proportion in the CT26-Treg co-culture system. SQYCD also promoted IL-2 levels while downregulating IL-10 and TGF-β levels. Mechanistically, SQYCD suppressed the IDO1/Kyn pathway and p-AKT expression. Additionally, components of SQYCD significantly reduced the IDO1-PI3K interaction. LC-MS and molecular docking results suggested that esculetin, glycitin, and hydroxygenkwanin may be the active components of SQYCD that reduce the IDO1-PI3K interaction.
SQYCD reduces Treg infiltration by inhibiting both the IDO1/Kyn/p-AKT and the IDO1-PI3K interaction, consequently enhancing the efficacy of ICIs.

PMID:
42869393
Bibliographic data and abstract were imported from PubMed on 14 Oct 2026.

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