Showing papers by "Sandra O. Gollnick published in 2022"

First-In-Human Computer-Optimized Endobronchial Ultrasound-Guided Interstitial Photodynamic Therapy for Patients With Extrabronchial or Endobronchial Obstructing Malignancies

Abstract: Patients with inoperable extrabronchial or endobronchial tumors who are not candidates for curative radiotherapy have dire prognoses with no effective long-term treatment options. To reveal that our computer-optimized interstitial photodynamic therapy (I-PDT) is safe and potentially effective in the treatment of patients with inoperable extra or endobronchial malignancies inducing central airway obstructions.High-spatial resolution computer simulations were used to personalize the light dose rate and dose for each tumor. Endobronchial ultrasound with a transbronchial needle was used to place the optical fibers within the tumor according to an individualized plan. The primary and secondary end points were safety and overall survival, respectively. An exploratory end point evaluated changes in immune markers.Eight patients received I-PDT with planning, and five of these received additional external beam PDT. Two additional patients received external beam PDT. The treatment was declared safe. Three of 10 patients are alive at 26.3, 12, and 8.3 months, respectively, after I-PDT. The treatments were able to deliver a prescribed light dose rate and dose to 87% to 100% and 18% to 92% of the tumor volumes, respectively. A marked increase in the proportion of monocytic myeloid-derived suppressor cells expressing programmed death-ligand 1 was measured in four of seven patients.Image-guided light dosimetry for I-PDT with linear endobronchial ultrasound transbronchial needle is safe and potentially beneficial in increasing overall survival of patients. I-PDT has a positive effect on the immune response including an increase in the proportion of programmed death-ligand 1-expressing monocytic myeloid-derived suppressor cells.

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

Abstract: 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.