Ceramide mediates FasL-induced caspase 8 activation in colon carcinoma cells to enhance FasL-induced cytotoxicity by tumor-specific cytotoxic T lymphocytes

• DOI: 10.1038/srep30816
• Publication Date: 2016-08-04T09:25:02Z
• Authors: Genevieve L. Coe; Priscilla S. Redd; Amy V. Paschall; Chunwan Lu; Lilly Gu; Houjian Cai; Thomas Albers; Iryna O. Lebedyeva; Kebin Liu
• Keywords: Fas ligand; Colon carcinoma; Caspase 8

FasL-mediated cytotoxicity is one of the mechanisms that CTLs use to kill tumor cells. However, human colon carcinoma often deregulates Fas signaling pathway evade host cancer immune surveillance. We aimed at testing hypothesis novel ceramide analogs effectively modulate function sensitize cells FasL-induced apoptosis. used rational design and synthesized twenty as modulators. Five analogs, IG4, IG7, IG14, IG17, IG19, exhibit low toxicity potent activity in sensitization Functional deficiency limits both FasL induction Ceramide enhances activation MAPK, NF-κB, caspase 8 despite cell death. Finally, a sublethal dose several significantly increased CTL-mediated apoptosis have therefore developed five act enhance efficacy tumor-specific CTLs, these hold great promise for further development adjunct agents CTL-based immunotherapy.