Document Type

Article

Publication Date

12-2019

Publication Title

Cancers

Volume

11

Pages

2034 (1-18)

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.

Comments

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

Original Publication Citation

Rossi, A., N Pakhomova, O., Mollica, P. A., Casciola, M., Mangalanathan, U., G Pakhomov, A., & Muratori, C. (2019). Nanosecond pulsed electric fields induce endoplasmic reticulum stress accompanied by immunogenic cell death in murine models of lymphoma and colorectal cancer. Cancers, 11, 2034. doi:10.3390/cancers11122034

ORCID

0000-0003-4950-4130, (Pakhomova), 0000-0002-0621-2819 (Mollica), 0000-0003-3816-3860 (Pakhomov), 0000-0002-3359-164X (Muratori)

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