Oral Presentation 18th International Congress on Photobiology 2024

Advancing Glioma Immunotherapy: Photodynamic Therapy-Induced Immunogenic Cell Death and Dendritic Cell Vaccines   (#130)

Dmitri Krysko 1 , Maria Vedunova 2 , Tatiana Mishchenko 2
  1. Cell Death Investigation and Therapy Laboratory, Ghent University, Ghent, Belgium
  2. National Research Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia

Gliomas, the most frequent type of primary tumor of the central nervous system in adults, results in significant morbidity and mortality. Despite the development of novel, complex, multidisciplinary, and targeted therapies, glioma therapy has not progressed much over the last decades. Therefore, there is an urgent need to develop novel patient-adjusted immunotherapies that actively stimulate antitumor T cells, generate long-term memory, and result in significant clinical benefits.

Immunogenic cell death (ICD) plays a pivotal role in triggering immune responses essential for effective anti-cancer therapies. A critical aspect of ICD is achieving a balanced combination of adjuvanticity and antigenicity. Adjuvanticity involves the release of damage-associated molecular patterns (DAMPs) primarily derived from dying cancer cells. These DAMPs, along with cytokines and chemokines, serve as adjuvants facilitating the recruitment and maturation of antigen-presenting cells. However, the presence of these adjuvant DAMPs signals alone is not sufficient to elicit an effective immune response against cancer cells. The cancer cells must also possess strong antigenic properties. Antigenicity is mediated by tumor-associated antigens predominantly presented by dendritic cells, particularly by the generation of neo-epitopes. Many anticancer agents and strategies induce ICD, but despite their robust effects in vitro and in vivo on mice, translation into the clinic remains challenging.

Therefore, in this work the therapeutic efficacy and molecular mechanisms responsible for the generation of anti-tumor immunity generated by dendritic cell (DC) vaccines loaded with ICD glioma lysates have been investigated. ICD has been induced by photosens-based photodynamic therapy. Here, I will first discuss the main principles of ICD, and then I will discuss the intriguing results obtained on orthotopic intracranial vaccination glioma mouse models. This work demonstrates the therapeutic feasibility of using DC vaccines loaded with glioma cells undergoing ICD and will open promising avenues for the development of novel immunotherapy for glioma.

Acknowledgments

The CDIT Laboratory is supported by the Flanders Research Foundation (FWO) and the Belgian National Fund for Scientific Research (F.R.S.-FNRS) under the Excellence of Science (EOS) program (40007488), FWO grant (G016221N), Special Research Fund (BOF) grants from Ghent University (BOF/IOP01/O3618, BOF/IOP/2022/ 033, BOF23/GOA/029), and IOF grants from Ghent University (‘PULSE’ F2023/IOF-ConcepTT/033 and ‘IMMUNO-FER-GUARD’ F2023/IOF-ConcepTT/106). TM and MV are supported by RSF (project no. 22–15-00376, https://rscf.ru/en/project/22-15-00376/).