Photodynamic therapy as immunogenic cell stress agent

Photodynamic therapy (PDT) is widely recognized as a modality capable of eliciting a strong immune reaction against treated tumors. This particular attribute has been actively studied for more than four decades yielding constantly advances in the understanding of the nature of immune responses induced with PDT and the underlying action mechanisms. Critical for this knowledge is the perception of PDT as an immunogenic cell stress agent. PDT-induced oxidative stress is recognized as directly responsible for the responses ranging from regulated immunogenic cell death (ICD) to immunogenic modulation. The PDT-elicited activity in stress signaling networks need to be in the focus of critical experimental approaches. In ICD, PDT-triggered stress pathways orchestrate release of antigens and danger signals from the dying tumor cells that enable the activation of adaptive antitumor immune response. The provided critical adjuvant signals come in the form of damage-associated molecular patterns (DAMPs) that are responsible for the recruitment and maturation of antigen-presenting cells (APCs). On the other hand, the immunogenic modulation enables enhanced antigen presentation, increased pro-apoptotic signals, changes in the expression of surface flag molecules by the tumor cells, and other tumor phenotype alterations making tumor more sensitized to the attack of T cell effectors. PDT can be clinically exploited as immunogenic cell stress agent for treatment of cancerous lesions either using adjuvants that can amplify the elicited immune responses or block negative immunoregulatory responses in tumor microenvironment.