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

Abstract

Liver X receptor (LXR) agonists inhibit various types of tumor growth and have been applied to preclinical research. In colon cancer cells, LXR agonists induce pyroptotic cell death through the predominant cytoplasmic localisation of LXRβ. In the present study, we determined whether tumor cell death induced by LXR agonists in colon cancer cells could elicit immunogenic cell death (ICD). LXR agonist-treated-colon cancer cells exhibited translocation of calreticulin (CRT) and release of HMGB1 and ATP into the medium. Expression levels of CRT and HMGB1 were also increased in T0901317-treated Balb/c mice. Furthermore, compared with control mice, mice vaccinated with T0901317-treated CT26 cells showed reduced tumor volumes and protection against a challenge with live tumor cells. Inhibition of CRT or HMGB1 expression in CT26 cells abolished this protection in Balb/c mice. In conclusion, the LXR agonist T0901317 induces ICD in colon cancer cells. CRT exposure and HMGB1 release play a critical role in the immunogenicity of this treatment.