2. Academic Validation
  3. Triptolide impacts CSF1R expression and reprograms the suppressive function of myeloid-derived suppressor cells via targeting the ER stress pathway

Triptolide impacts CSF1R expression and reprograms the suppressive function of myeloid-derived suppressor cells via targeting the ER stress pathway

  • Cytokine. 2026 Jan:197:157068. doi: 10.1016/j.cyto.2025.157068.
Huijie Huang 1,  Guojun Liang 1,  Yaozong He 1,  Hongyu Wang 2,  Xiaowen Lin 3,  Ziling Zhao 1,  Enyu Liang 1,  Yunxiu Wang 1,  Jian-Xin Peng 4,  Hong-Wei Sun 5,  Min He 6
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 2 State Key Laboratory of Dampness Syndrome of Chinese Medicine, the Second Affiliated Hospitals of Guangzhou University of Chinese Medicine, Guangzhou, China; Guangdong Provincial Key laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; Department of Interventional Therapy, the Second Affiliated Hospitals of Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 3 Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital, Zhuhai, China.
  • 4 Department of Hepatobiliary Surgery, the Second Affiliated Hospitals of Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 5 Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital, Zhuhai, China. Electronic address: [email protected].
  • 6 Department of Laboratory Medicine, the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China; State Key Laboratory of Dampness Syndrome of Chinese Medicine, the Second Affiliated Hospitals of Guangzhou University of Chinese Medicine, Guangzhou, China; Guangdong Provincial Key laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address: [email protected].
PMID: 41197245 DOI: 10.1016/j.cyto.2025.157068
Abstract

Triptolide (TPT) is a natural compound in herbal remedies with anti-inflammatory and anti-tumor properties. The study aimed to investigate the therapeutic effect of triptolide treatment on Myeloid-derived suppressor cells (MDSCs) in Hepatocellular Carcinoma (HCC). Single-cell transcriptomic profiling of liver tumor biopsies identified (Colony-Stimulating Factor 1 Receptor) CSF1R+ MDSCs as a distinct MDSCs lineage in HCC patients, which exhibited a positive correlation with the severity of HCC. Flow cytometric analysis confirmed CSF1R+ MDSCs were enriched in the peripheral blood and tumor tissue of HCC patients. Elevated CSF1R expression were highly expressed on the polymorphonuclear-MDSCs (PMN-MDSCs) subset specifically. Notably, PERK-mediated endoplasmic reticulum (ER) stress activation contributed to CSF1R induction, as evidenced by inhibiting the activities of PERK, but not IRE1α or ATF6, successfully attenuated the frequency of CSF1R+ MDSCs. Moreover, TPT dose-dependently diminished MDSCs and CSF1R+ MDSCs frequencies, alongside with alleviating the immunosuppressive capability on T cell proliferation. Further investigation revealed TPT treatment suppressed phosphorylation of PERK, as well as the protein levels of ATF4 and C/EBPβ. Our results underscore the role of ER stress-induced CSF1R expression in driving HCC disease progression by promoting the immunosuppressive effects of MDSCs, and identify CSF1R as a promising immunosuppressive target of TPT in HCC therapy.

Keywords

Colony-stimulating factor 1 receptor; Endoplasmic reticulum stress; Hepatocellular carcinoma; Myeloid-derived suppressor cells; Triptolide.

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