Me-ALA based photodynamic therapy as a novel putative immunogenic cell death inducer against melanoma

LAMBERTI MJ; MENTUCCI FM; GATTI GA; MACCIONI M; RIVAROLA VA

Sao Paulo

Otro; IUIS-Brazil Advanced Course on Vaccines; 2017

The immunogenicity of tumor cells has recently been acknowledgedas a critical determinant of efficacy in cancer therapy. It isnow clear that cancer cells can succumb to some anticancer therapiesby undergoing a peculiar form of cell death that is characterizedby the emission of damage/associated molecular patterns(DAMPs). The release of DAMPs and other immunostimulatoryfactors by cells dying through immunogenic cell death (ICD) favorsthe establishment of a productive interface with the immune system.The purpose of the present study was to evaluate the effectivenessof the PS protoporphyrin IX (PpIX) in promoting the exposure ofpivotal DAMPs that characterize ICD, such as calreticulin (CRT),on melanoma cells. B16-OVA cells were sensitized with Me-ALAinducedPpIX during 4 h. Interestingly, confocal microscopy imagesshowed that PpIX was preferentially localized in the endoplasmicreticulum (ER) prior to irradiation (Pearson?s r: 0.934). Subsequentphotoactivation of PpIX with lethal dose significantly promoted oxidativestress (100% DCF + cells). ROS-scavenger N-acetylcysteine(NAC) inhibited cytotoxic effect of PDT by 33.3% (p