期刊
AUTOPHAGY
卷 9, 期 9, 页码 1292-1307出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/auto.25399
关键词
autophagy; calreticulin; ATP; immunogenic cell death; T cells; cancer; photodynamic therapy (PDT); dendritic cells
类别
资金
- Fund for Scientific Research Flanders (FWO-Vlaanderen) [G.0661.09, G.0728.10, G.0584.12N]
- KU Leuven [GOA/11/009]
- BOF Postdoctoral Mandate (PDM) from KU Leuven [PDMK/12/146]
- FWO
- Interuniversity Attraction Poles Programme
- Belgian State, Science Policy Office
- FWO-Vlaanderen [G.0728.10, 31507110]
- FWO-Vlaanderen
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 prerequisites or determinants.
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