Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Immunol. Nov 27, 2015; 5(3): 95-98
Published online Nov 27, 2015. doi: 10.5411/wji.v5.i3.95
Impact of cell death manipulation on the efficacy of photodynamic therapy-generated cancer vaccines
Mladen Korbelik
Mladen Korbelik, Department of Integrative Oncology, British Columbia Cancer Agency, Vancouver V5Z 1L3, Canada
Author contributions: Korbelik M designed the described research, analyzed the data and wrote the paper.
Supported by The Canadian Cancer Society, No. # 701132.
Conflict-of-interest statement: The author has no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Mladen Korbelik, Department of Integrative Oncology, British Columbia Cancer Agency, 675 West 10th Avenue, Vancouver BC, V5Z 1L3, Canada. mkorbelik@bccrc.ca
Telephone: +1-604-6758084 Fax: +1-604-6758099
Received: May 10, 2015
Peer-review started: May 10, 2015
First decision: June 18, 2015
Revised: July 9, 2015
Accepted: July 29, 2015
Article in press: August 3, 2015
Published online: November 27, 2015
Processing time: 201 Days and 9.7 Hours
Abstract

The main task of cancer vaccines is to deliver tumor-specific antigens to antigen-presenting cells for immune recognition that can lead to potent and durable immune response against treated tumor. Using photodynamic therapy (PDT)-generated vaccines as an example of autologous whole-cell cancer vaccines, the importance is discussed of the expression of death-associated molecules on cancer vaccine cells. This aspect appears critical for the optimal capture of vaccine cells by host’s sentinel phagocytes in order that the tumor antigenic material is processed and presented for immune recognition and elimination of targeted malignancy. It is shown that changing death pattern of vaccine cells by agents modulating apoptosis, autophagy or necrosis can significantly alter the therapeutic impact of PDT-generated vaccines. Improved therapeutic effect was observed with inhibitors of necrosis/necroptosis using IM-54, necrostatin-1 or necrostatin-7, as well as with lethal autophagy inducer STF62247. In contrast, reduced vaccine potency was found in case of treating vaccine cells with apoptosis inhibitors or lethal autophagy inhibitor spautin-1. Therefore, PDT-generated cancer vaccine cells undergoing apoptosis or lethal autophagy are much more likely to produce therapeutic benefit than vaccine cells that are necrotic. These findings warrant further detailed examination of the strategy using cell death modulating agents for the enhancement of the efficacy of cancer vaccines.

Keywords: Antitumor immune response; Photodynamic therapy-generated vaccines; Cell death; Endoplasmic reticulum stress response; Reticular unfolded proteins response; Damage-associated molecular patterns; Immunogenic cell death

Core tip: It is discussed how the mode of cell death can be important to the efficacy of cancer vaccine, using the example of photodynamic therapy-generated whole-cell vaccines. With the example of several agents modulating apoptosis, necrosis or autophagy, it is argued that the strategy of using such agents for the enhancement of the efficacy of cancer vaccines deserves serious consideration.