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Nanosecond pulsed electric fields induce endoplasmic reticulum stress accompanied by immunogenic cell death in murine models of lymphoma and colorectal cancer
- Source :
- Cancers, Volume 11, Issue 12
- Publication Year :
- 2019
- Publisher :
- MDPI, 2019.
-
Abstract
- Depending on the initiating stimulus, cancer cell death can be immunogenic or non-immunogenic. Inducers of immunogenic cell death (ICD) rely on endoplasmic reticulum (ER) stress for the trafficking of danger signals such as calreticulin (CRT) and ATP. We found that nanosecond pulsed electric fields (nsPEF), an emerging new modality for tumor ablation, cause the activation of the ER-resident stress sensor PERK in both CT-26 colon carcinoma and EL-4 lymphoma cells. PERK activation correlates with sustained CRT exposure on the cell plasma membrane and apoptosis induction in both nsPEF-treated cell lines. Our results show that, in CT-26 cells, the activity of caspase-3/7 was increased fourteen-fold as compared with four-fold in EL-4 cells. Moreover, while nsPEF treatments induced the release of the ICD hallmark HMGB1 in both cell lines, extracellular ATP was detected only in CT-26. Finally, in vaccination assays, CT-26 cells treated with nsPEF or doxorubicin equally impaired the growth of tumors at challenge sites eliciting a protective anticancer immune response in 78% and 80% of the animals, respectively. As compared to CT-26, both nsPEF- and mitoxantrone-treated EL-4 cells had a less pronounced effect and protected 50% and 20% of the animals, respectively. These results support our conclusion that nsPEF induce ER stress, accompanied by bona fide ICD.
- Subjects :
- electroporation
Cancer Research
biology
Chemistry
medicine.medical_treatment
Endoplasmic reticulum
apoptosis
Immunotherapy
ablation
Article
immunotherapy
vaccine
Oncology
Apoptosis
Cell culture
Cancer cell
Cancer research
medicine
Unfolded protein response
biology.protein
Immunogenic cell death
Calreticulin
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cancers, Volume 11, Issue 12
- Accession number :
- edsair.doi.dedup.....ad40e5c62cdb256ebf384e4f49183a34