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An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
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Small-molecule inhibitor sorafenib regulates immunoreactions by inducing survival and differentiation of bone marrow

Xiangxuan Zhao1, Mengde Cao2, Zaiming Lu3

  • 1Department of Radiology, China Medical University Shengjing Hospital, Shenyang, China Department of Pathology, University of Florida College of Medicine, Gainesville, FL, USA Institute of Cancer Stem Cell, Dalian Medical University Cancer Center, Dalian, China zhaoxiangxuan@163.com xiangxuanzhao@163.com.

Innate Immunity
|July 22, 2016
PubMed

Insights

Low doses of sorafenib, a liver cancer drug, promote bone marrow cell survival and create immune-suppressing dendritic cells. This reveals sorafenib

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • Sorafenib is a known treatment for liver cancer.
  • Its effects on the human immune system are not well understood.
  • Previous research indicated sorafenib modulates immunosuppressive cells in mouse models.

Purpose of the Study:

  • To investigate the immunomodulatory effects of sorafenib at low doses.
  • To determine sorafenib's impact on bone marrow cells and dendritic cell differentiation.

Main Methods:

  • Treatment of murine bone marrow cells (BMCs) with varying doses of sorafenib.
  • Analysis of BMC survival, apoptosis (survivin expression), and differentiation.
  • Characterization of sorafenib-induced dendritic cells and their effect on T-cell responses (cytokine production, proliferation).

Main Results:

  • Low-dose sorafenib promoted BMC survival in a dose-dependent manner via survivin.
  • Sorafenib induced BMC differentiation into suppressive dendritic cells.
  • These dendritic cells inhibited T-cell proliferation and altered cytokine profiles (increased IL-1β, IL-2, IL-4, IL-10, IFN-γ, TNF-α; decreased IL-6, CD25).

Conclusions:

  • Sorafenib exhibits immunoregulatory properties at low doses, beyond its anticancer effects.
  • Sorafenib-induced dendritic cells represent a unique subset with distinct suppressive functions.
  • These findings highlight the complex interplay between sorafenib and the immune system.
Keywords:
SorafenibT cellsbone marrow cellsdendritic cellsimmunoreaction

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