Title: ROS-induced autophagy in cancer cells assists in evasion from determinants of immunogenic cell death
Authors: Garg, Abhishek
Dudek, Aleksandra
Ferreira, Gabriela B
Verfaillie, Tom
Vandenabeele, Peter
Krysko, Dmitri V
Mathieu, Chantal
Agostinis, Patrizia # ×
Issue Date: Sep-2013
Publisher: Landes Bioscience
Series Title: Autophagy vol:9 issue:9 pages:1292-307
Abstract: Calreticulin surface exposure (ecto-CALR), ATP secretion, maturation of dendritic cells (DCs) and stimulation of T cells are prerequisites for anticancer therapy-induced immunogenic cell death (ICD). Recent evidence suggests that chemotherapy-induced autophagy may positively regulate ICD by favoring ATP secretion. We have recently shown that reactive oxygen species (ROS)-based endoplasmic reticulum (ER) stress triggered by hypericin-mediated photodynamic therapy (Hyp-PDT) induces bona fide ICD. However, whether Hyp-PDT-induced autophagy regulates ICD was not explored. Here we showed that, in contrast to expectations, reducing autophagy (by ATG5 knockdown) in cancer cells did not alter ATP secretion after Hyp-PDT. Autophagy-attenuated cancer cells displayed enhanced ecto-CALR induction following Hyp-PDT, which strongly correlated with their inability to clear oxidatively damaged proteins. Furthermore, autophagy-attenuation in Hyp-PDT-treated cancer cells increased their ability to induce DC maturation, IL6 production and proliferation of CD4 (+) or CD8 (+) T cells, which was accompanied by IFNG production. Thus, our study unravels a role for ROS-induced autophagy in weakening functional interaction between dying cancer cells and the immune system thereby helping in evasion from ICD pre-requisites or determinants.
ISSN: 1554-8627
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Cell Death Research & Therapy
Clinical and Experimental Endocrinology
× corresponding author
# (joint) last author

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