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Treatment of colon cancer with liver X receptor agonists induces immunogenic cell death

Qiang Wang1, Meijia Ren1, Fan Feng2

  • 1Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu, China.

Molecular Carcinogenesis
|March 25, 2018
PubMed

Insights

Liver X receptor (LXR) agonists trigger immunogenic cell death (ICD) in colon cancer cells, marked by calreticulin exposure and HMGB1 release. This immune response reduces tumor growth and protects against cancer challenges in preclinical models.

Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • Liver X receptor (LXR) agonists show promise in inhibiting tumor growth.
  • LXR agonists induce pyroptotic cell death in colon cancer cells via cytoplasmic LXRβ localization.

Purpose of the Study:

  • To investigate if LXR agonists induce immunogenic cell death (ICD) in colon cancer cells.
  • To determine the role of calreticulin (CRT) and HMGB1 in LXR agonist-induced ICD and anti-tumor immunity.

Main Methods:

  • Treatment of colon cancer cells and Balb/c mice with LXR agonist T0901317.
  • Assessment of CRT translocation, HMGB1 and ATP release, and CRT/HMGB1 expression levels.
  • Tumor growth inhibition and protection studies in mice vaccinated with treated cancer cells, including experiments with inhibited CRT/HMGB1 expression.

Main Results:

  • LXR agonist treatment led to CRT translocation and HMGB1/ATP release from colon cancer cells, indicative of ICD.
  • Increased CRT and HMGB1 expression was observed in T0901317-treated mice.
  • Vaccination with treated CT26 cells reduced tumor volume and provided protection against tumor cell challenge in mice.
  • Inhibition of CRT or HMGB1 abolished the protective effect, highlighting their critical role.

Conclusions:

  • The LXR agonist T0901317 effectively induces immunogenic cell death (ICD) in colon cancer cells.
  • CRT exposure and HMGB1 release are crucial mechanisms mediating the anti-tumor immune response elicited by LXR agonists.
Keywords:
CRT exposure and HMGB1 releaseimmunogenic cell deathliver X receptors

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