Targeting Epigenetic Processes in Photodynamic Therapy-Induced Anticancer Immunity
Malgorzata Wachowska1, Angelika Muchowicz1, Jakub Golab1
1Department of Immunology, Medical University of Warsaw , Warsaw , Poland.
Abstract:
Photodynamic therapy (PDT) of cancer is an approved therapeutic procedure that generates oxidative stress leading to cell death of tumor and stromal cells. Cell death resulting from oxidative damage to intracellular components leads to the release of damage-associated molecular patterns (DAMPs) that trigger robust inflammatory response and creates local conditions for effective sampling of tumor-associated antigens (TAA) by antigen-presenting cells. The latter can trigger development of TAA-specific adaptive immune response. However, due to a number of mechanisms, including epigenetic regulation of TAA expression, tumor cells evade immune recognition. Therefore, numerous approaches are being developed to combine PDT with immunotherapies to allow development of systemic immunity. In this review, we describe immunoregulatory mechanisms of epigenetic treatments that were shown to restore the expression of epigenetically silenced or down-regulated major histocompatibility complex molecules as well as TAA. We also discuss the results of our recent studies showing that epigenetic treatments based on administration of methyltransferase inhibitors in combination with PDT can release effective mechanisms leading to development of antitumor immunity and potentiated antitumor effects.
Insights
Photodynamic therapy (PDT) combined with epigenetic treatments can overcome tumor immune evasion. This approach restores tumor antigen presentation, enhancing antitumor immunity and therapeutic effects.
Area of Science:
- Oncology
- Immunology
- Epigenetics
Background:
- Photodynamic therapy (PDT) induces cancer cell death and inflammation, releasing damage-associated molecular patterns (DAMPs) that can prime anti-tumor immune responses.
- Tumor cells often evade immune recognition through mechanisms like epigenetic silencing of tumor-associated antigens (TAA) and MHC molecules.
- Combining PDT with immunotherapies is a promising strategy to overcome immune evasion and induce systemic anti-tumor immunity.
Purpose of the Study:
- To review the immunoregulatory mechanisms of epigenetic treatments in conjunction with PDT.
- To discuss how epigenetic therapies can restore the expression of silenced TAAs and major histocompatibility complex (MHC) molecules.
- To present findings on the combination of PDT with methyltransferase inhibitors for enhanced anti-tumor immunity.
Main Methods:
- Review of existing literature on PDT, epigenetic modifications, and cancer immunotherapy.
- Analysis of studies investigating the restoration of TAA and MHC expression via epigenetic modulation.
- Evaluation of preclinical data on the combination of PDT with methyltransferase inhibitors.
Main Results:
- Epigenetic treatments can reverse the silencing of TAAs and MHC molecules, improving antigen presentation.
- The combination of PDT with methyltransferase inhibitors has demonstrated the ability to activate potent anti-tumor immune responses.
- Enhanced anti-tumor effects and the development of systemic immunity were observed in studies combining PDT and epigenetic therapies.
Conclusions:
- Epigenetic therapies hold significant potential for enhancing the efficacy of PDT by overcoming tumor immune escape mechanisms.
- Combining PDT with epigenetic agents, such as methyltransferase inhibitors, represents a viable strategy for generating robust and durable anti-tumor immunity.
- This combined approach offers a promising avenue for improving cancer treatment outcomes by harnessing the immune system.
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