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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00811

Low photosensitizer dose and early radiotherapy enhance antitumor immune response of photodynamic therapy-based dendritic cell vaccination

  • 1Pôle de Pharmacologie et de Thérapeutique, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Belgium
  • 2Institute of Condensed Matter and Nanosciences, Catholic University of Louvain, Belgium

Recent studies have highlighted the potential of photodynamic therapy (PDT) to induce immunogenic cell death (ICD). The clinical use of photosensitizers (PS) to stimulate an anticancer immune response, and not to sterilize tumor cells, may however require some optimizations. Here, we examined how the dose of PS and the scheduling of PDT influence the generation of danger-associated molecular patterns proteins (DAMPs) and favor T cell antitumor activity. We found that upon photoactivation, a low dose of the non-porphyrinic PS OR141 was more prone than higher doses to induce DAMPs in vitro and to inhibit squamous cell carcinoma growth in mice. We further used PDT-killed cancer cells to prime dendritic cells (DC) and stimulate their maturation to evaluate whether the timing of their injection could influence the antitumor effects of radiotherapy. While PDT-based DC vaccination administered before radiotherapy failed to increase tumor growth inhibition, DC injection in the peri-radiotherapy period led to significant tumor growth delay, emphasizing the importance of the coincidence of T cell activation and alterations of the tumor bed. In conclusion, the use of OR141 as a bona fide ICD inducer led us to unravel both the non-linear relationship between PS concentration and PDT-induced antitumor immune response, and the value of an optimal timing of PDT when co-administered with conventional anticancer therapies. This study therefore stresses the necessity of adapting the clinical use of PDT when the goal is to promote an immune response and identifies PDT-based DC vaccination as a suitable modality to reach such objective.

Keywords: Photodynamic therapy (PDT), Immunogenic cell death (ICD), danger-associated molecular patterns (DAMPs), Radiotherapy, Vaccination

Received: 01 Jul 2019; Accepted: 08 Aug 2019.

Edited by:

Marie-Odile Parat, University of Queensland, Australia

Reviewed by:

Dmitri V. Krysko, Ghent University, Belgium
Michael R. Hamblin, Massachusetts General Hospital, Harvard Medical School, United States  

Copyright: © 2019 Doix, Trempolec, Riant and Feron. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Olivier Feron, Pôle de Pharmacologie et de Thérapeutique, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium, olivier.feron@uclouvain.be