PDT-associated host response and its role in the therapy outcome

Background and Objectives: The outcome of the treatment of solid tumors by photodynamic therapy (PDT) is critically dependent on the contribution from the host. This host response is provoked by the rapidly induced massive tumor tissue injury delivered by PDT that is experienced as a local trauma threatening the integrity and homeostasis at the affected site. Study Design/Materials and Methods: Mouse tumor models were extensively employed in pre-clinical studies investigating various aspects of host-tumor interaction following PDT, but important input was also derived from clinical data. Results: The recognition of this PDT-inflicted insult by innate immune sensors detecting danger signals from the distressed/altered tumor tissue, triggers host-protecting responses dominantly manifested as acute inflammation that are elicited and orchestrated by the innate immune system. To secure the affected PDT-targeted site, the inflammatory reaction attacks tumor vasculature and then neutralizes the focal source of danger signals by eliminating the injured tumor cells. Conclusion: The provoked highly intensified phagocytosis of dead tumor cells occurring in the context of a vigorous innate immune reaction emerges as a key factor responsible for the development of tumor antigen-specific adaptive immune response that contributes to the eradication of PDT-treated cancers.