Targeting Epigenetic Processes in Photodynamic Therapy-Induced Anticancer Immunity

TL;DR

This review explores how combining photodynamic therapy with epigenetic treatments can enhance anticancer immunity by restoring immune recognition of tumor cells.

Contribution

The paper introduces how epigenetic treatments, like methyltransferase inhibitors, can boost PDT's effectiveness by reactivating immune-related genes.

Findings

Epigenetic treatments can restore expression of silenced major histocompatibility complex molecules and tumor-associated antigens.

Combining PDT with methyltransferase inhibitors enhances antitumor immunity and improves therapeutic outcomes.

Epigenetic regulation plays a key role in tumor immune evasion and can be targeted to improve immunotherapy.

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.

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