Photodynamic therapy in the trap of resistance: a path to overcoming through the induction of immunogenic cell death
Ekaterina Sleptsova 1, Alina Khuzina 1, Daria Sachkova 2,3, Diana Yuzhakova 2, Yevgeniya Sannova 1, Konstantin Yashin 4, Nina Peskova 3, Svetlana Lermontova 5, Ilya Shchechkin 2,6, Larisa Klapshina 5,
Irina Balalaeva 3 and Victoria Turubanova 1,7; 1. Department of Genetics and Life Sciences, Sirius University, Sochi, Russia; 2. Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russia; 3. Institute of Biology and Biomedicine, Lobachevsky State University, Nizhny Novgorod, Russia; 4. Department of Neurosurgery, Privolzsky Research Medical University, Nizhny Novgorod, Russia; 5. Sector of Chromophors for Medicine, G.A. Razuvaev Institute of Organometallic Chemistry of the Russian Academy of Sciences, Nizhny Novgorod, Russia; 6. Institute of Information Technology, Mathematics and Mechanics, Lobachevsky State University, Nizhny Novgorod, Russia; 7. Institute of Neurosciences, Lobachevsky State University, 603022 Nizhny Novgorod, Russia
Abstract
Despite photodynamic therapy (PDT) occupying a significant place among cancer treatment modalities, its efficacy remains fundamentally constrained by its local mechanism of action and the development of tumor cell resistance. The aim of our work is to analyze the biological consequences of PDT in primary human glioma cultures. We summarize current knowledge on the molecular and cellular mechanisms of PDT and explore strategies to overcome its inherent limitations through the application of immunotherapeutic approaches.
Particular attention is paid to the critical role of switching from non-immunogenic to immunogenic cell death in shaping an effective antitumor response. In this study, we investigated the features of regulated cell death induced by PDT using a previously described inducer of immunogenic cell death (ICD) — porphyrazine III (tetra(aryl)tetracyanoporphyrazine). Cell death was studied in primary cultures of high-grade human gliomas (astrocytomas, oligodendrogliomas, and glioblastomas).
We examined the localization of the photosensitizer and the relationship between this factor and the production of different types of reactive oxygen species (ROS) as well as the mode of regulated cell death. A narrow concentration window of porphyrazine III was established for effectively achieving IC85, which primarily induces ferroptosis with contributions from apoptosis and necroptosis, accompanied by superoxide anion generation and mitochondrial dysfunction.
We propose that strategies based on dendritic cell vaccination hold potential for inducing specific antitumor immunity against aggressive malignancies, while emphasizing the unique advantages of dendritic cell vaccines in mitigating the key shortcomings of conventional PDT.
Speaker
Victoria Tururbanova
Sirius University, Institute of Neurosciences Lobachevsky State University
Russia
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