Trial watch: an update of clinical advances in photodynamic therapy and its immunoadjuvant properties for cancer treatment

Photodynamic therapy (PDT) is a medical treatment used to target solid tumors, where the administration of a photosensitizing agent and light generate reactive oxygen species (ROS), thus resulting in strong oxidative stress that selectively damages the illuminated tissues. Several preclinical studies have demonstrated that PDT can prime the immune system to recognize and attack cancer cells throughout the body. However, there is still limited evidence of PDT-mediated anti-tumor immunity in clinical settings. In the last decade, several clinical trials on PDT for cancer treatment have been initiated, indicating that significant efforts are being made to improve current PDT protocols. However, most of these studies disregarded the immunological dimension of PDT. The immunomodulatory properties of PDT can be combined with standard therapy and/or emerging immunotherapies, such as immune checkpoint blockers (ICBs), to achieve better disease control. Combining PDT with immunotherapy has shown synergistic effects in some preclinical models. However, the value of this combination in patients is still unknown, as the first clinical trials evaluating the combination of PDT with ICBs are just being initiated. Overall, this Trial Watch provides a summary of recent clinical information on the immunomodulatory properties of PDT and ongoing clinical trials using PDT to treat cancer patients. It also discusses the future perspectives of PDT for oncological indications.