Immunogenic cell death induced by PDT : a new approach for cancer therapy

Immunotherapy has become an important part in cancer treatment during the last decade. One of the major factors for induction of immune response during therapy is immunogenic cell death (ICD) (1). The immunogenicity of dying cancer cells is mediated by their adjuvanticity and antigenicity. Damage-associated molecular patterns (DAMPs) are endogenous molecules located inside the cells and in normal conditions contribute to different physiological processes while they are released (or exposed on the outer surface of the plasma membrane) when a cell is damaged or dying. Once released, DAMPs acquire immunostimulatory properties and increase the adjuvanticity of dying cancer cells. Of course, DAMPs are not the only factors released during cell death that are involved in their adjuvanticity. Antigenicity of dying cancer cells is another major determinant of ICD which is required for an efficiently targeted induction of anti-tumor immunity. ICD can be induced by different stimuli and anticancer treatment modalities, including chemotherapy with anthracyclines and oxaliplatin, radiotherapy, UVC irradiation, oncolytic viruses, and photodynamic therapy (PDT) (2). The ICD induced by various stimuli can differ in the DAMPs’ profile and has also been linked to different cell death modalities such as apoptosis, necroptosis and ferroptosis (3). Thus, in this lecture, we first discuss the role of PDT in the induction of ICD (4) and then assess the advantages and disadvantages of PDT in the induction of ICD. Finally, we will discuss a possible synergistic action between PDT and ferroptotic cell death (5), a novel, iron-dependent form of regulated cell death6. PDT can act as a source of reactive oxygen species for the Fenton reaction, which may reinforce ferroptosis induction and increase PDT efficacy in anticancer therapy. References 1) Galluzzi, Vitale, et al. Consensus guidelines for the definition, detection and interpretation of immunogenic cell death. J Immunother Cancer. 2020. 2) Alzeibak, Mishchenko et al. Targeting immunogenic cancer cell death by photodynamic therapy: past, present and future. J Immunother Cancer. 2021. 3) Efimova, Catanzaro et al. Vaccination with early ferroptotic cancer cells induces efficient antitumor immunity. J Immunother Cancer. 2020. 4) Turubanova, Balalaeva et al. Immunogenic cell death induced by a new photodynamic therapy based on photosens and photodithazine. J Immunother Cancer 2019. 5) Mishchenko, Balalaeva et al. Ferroptosis and Photodynamic Therapy Synergism: Enhancing Anticancer Treatment. Trends Cancer. 2021. 6) Friedmann Angeli, Krysko et al. Ferroptosis at the crossroads of cancer-acquired drug resistance and immune evasion. Nat Rev Cancer. 2019