Photodynamic Therapy-Induced Cyclooxygenase 2 Expression in Tumor-Draining Lymph Nodes Regulates B-Cell Expression of Interleukin 17 and Neutrophil Infiltration.

Photodynamic therapy (PDT) is an effective anticancer modality approved by the U.S. Food and Drug Administration (FDA). Antitumor immunity can be augmented during PDT by inducing sterile inflammation in an acute manner, and this process is characterized by interleukin 17 (IL-17)-mediated neutrophil infiltration to tumor-draining lymph nodes (TDLNs). However, the inflammatory factors that influence IL-17 expression in TDLNs are poorly understood. Prior studies have linked the cyclooxygenase 2 (COX2)-driven prostaglandin E2 (PGE2) pathway to IL-17 expression. Here, we report that an immune-activating PDT regimen (imPDT) induces COX2/PGE2 expression in TDLNs, whereby IL-17 expression is facilitated without corresponding effects on the expression of RORγt, the transcriptional driver of the canonical IL-17 pathway. Pharmacologic inhibition with NS398, a COX2 inhibitor, was utilized to demonstrate that imPDT-induced COX2 regulates RORγt-independent expression of IL-17 by B cells and neutrophil entry into TDLNs. Depletion of B cells prior to imPDT significantly reduced neutrophil entry into TDLNs following treatment, and diminishes the efficacy of imPDT, which is dependent upon antitumor immunity. These findings are suggestive of a novel role for B cells in the augmentation of antitumor immunity by imPDT.

Photodynamic Therapy and Immunity: An Update.

Dr. Thomas Dougherty and his Oncology Foundation of Buffalo were the first to support my (S.O.G.) research into the effects of photodynamic therapy (PDT) on the host immune system. The small grant I was awarded in 2002 launched my career as an independent researcher; at the time, there were few studies on the importance of the immune response on the efficacy of PDT and no studies demonstrating the ability of PDT to enhance antitumor immunity. Over the last decades, the interest in PDT as an enhancer of antitumor immunity and our understanding of the mechanisms by which PDT enhances antitumor immunity have dramatically increased. In this review article, we look back on the studies that laid the foundation for our understanding and provide an update on current advances and therapies that take advantage of PDT enhancement of immunity.