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Micromanipulation of Circulating Tumor Cells for Downstream Molecular Analysis and Metastatic Potential Assessment
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Tumor cell-derived microparticles containing MTX (MTX-TMPs) in the treatment of cholangiocarcinoma by modulating

Qi Zhang1, Saifei Wang2, Bin Liu1

  • 1Hospital of Integrated Chinese and Western Medicine, Tianjin Medical University, Tianjin 300100, China; Institute of Integrative Medicine for Acute Abdominal Diseases, Tianjin 300100, China; Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin 300100, China.

Life Sciences
|May 21, 2025
PubMed
Abstract

Insights

MTX-TMPs effectively treat cholangiocarcinoma (CCA) by regulating myeloid-derived suppressor cells (MDSCs). This therapy enhances anti-tumor immunity and inhibits CCA progression, offering a promising strategy for liver cancer treatment.

Area of Science:

  • Oncology
  • Immunology
  • Biotechnology

Background:

  • Cholangiocarcinoma (CCA) is a prevalent liver cancer with limited treatment options.
  • Tumor cell-derived microparticles (TMPs) carrying MTX (MTX-TMPs) show potential in treating CCA by clearing bile duct obstruction.
  • The precise mechanism of MTX-TMPs in CCA treatment remains to be elucidated.

Purpose of the Study:

  • To investigate the therapeutic mechanism of MTX-TMPs in cholangiocarcinoma (CCA).
  • To evaluate the immunomodulatory effects of MTX-TMPs on myeloid-derived suppressor cells (MDSCs) in CCA.
  • To assess the impact of MTX-TMPs on CCA progression and immune cell populations.

Main Methods:

  • Analysis of liver function and immune cell profiles in CCA patients treated with MTX-TMPs.
  • Establishment of an intrahepatic cholangiocarcinoma (ICC) mouse model to study MTX-TMPs effects.
  • In vitro investigation of MTX-TMPs' impact on CCA cells and human/mouse MDSCs, focusing on inflammation, apoptosis, migration, and immunosuppression.

Main Results:

  • MTX-TMPs treatment increased beneficial immune cells (CD45+, CD4+ T, CD8+ T, NK, NKT) and decreased MDSCs in CCA patients without adverse liver effects.
  • In vivo studies showed MTX-TMPs alleviated ICC progression and reduced MDSC proportions.
  • In vitro, MTX-TMPs inhibited CCA cell pro-inflammatory factors, STAT3/NF-κB activation, promoted MDSC apoptosis, and suppressed MDSC recruitment, differentiation, and function via the STAT/CEBPβ pathway.

Conclusions:

  • MTX-TMPs demonstrate significant therapeutic efficacy in cholangiocarcinoma (CCA) by modulating myeloid-derived suppressor cells (MDSCs).
  • This mechanism involves inhibiting CCA cell pro-inflammatory signaling and directly impacting MDSC functions, including apoptosis and immunosuppression.
  • MTX-TMPs represent a novel and effective therapeutic strategy for CCA treatment by regulating the tumor immune microenvironment.
Keywords:
CholangiocarcinomaExtracellular vesiclesMTX-TMPsMyeloid-derived suppressor cellsTumor immune microenvironmentTumor immunology

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