Bremachlorin-Based Photodynamic-Therapy-Induced Effects in Low-Oxygenated Pancreatic Ductal Adenocarcinoma (PDAC) Tumor Microenvironment
4 affiliations
- 1Department of Radiology and Nuclear Medicine, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
- 2Department of Molecular Genetics, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
- 3Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
- 4Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands
Abstract
Photodynamic therapy (PDT) is a minimally invasive treatment whose efficacy is strongly influenced by tumor oxygenation and the tumor microenvironment (TME). Pancreatic ductal adenocarcinoma (PDAC) is characterized by severe hypoxia, dense stroma, and immune suppression, limiting therapeutic responsiveness. In this study, we investigated how Bremachlorin-based PDT remodels the TME in two murine PDAC models with distinct immune phenotypes (T-cell–high and T-cell–low) and compared them with the immunogenic MC38 colon carcinoma model. Single-fiber reflectance and fluorescence spectroscopy were used to monitor tumor physiology and photosensitizer dynamics during PDT, while multiplex immunohistochemistry enabled spatial profiling of stromal and immune components post-treatment. PDAC tumors exhibited significantly lower baseline oxygenation than MC38 tumors, which was not substantially improved by reducing the PDT fluence rate from 116 to 50 mW·cm−2. Nevertheless, PDT reduced collagen type I content in both PDAC models, indicating stromal remodeling. Importantly, illumination with a moderate fluence rate of 50 mW·cm−2 significantly increased CD8+ T-cell infiltration and improved the CD8+/neutrophil ratio in T-cell–high PDAC tumors, suggesting a shift toward a less immunosuppressive immune landscape. These findings demonstrate that Bremachlorin-PDT can modulate the PDAC tumor microenvironment and highlight the importance of immune context in shaping PDT outcomes, supporting rational optimization of PDT-based combination therapies.
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BibTeX
@article{mcmorrow2026bremachlorinbased,
title = {{Bremachlorin-Based Photodynamic-Therapy-Induced Effects in Low-Oxygenated Pancreatic Ductal Adenocarcinoma (PDAC) Tumor Microenvironment}},
author = {Roisin McMorrow and Henriette S. de Bruijn and Ivo Que and Karishma Lila and Thierry P. P. van den Bosch and Michail Doukas and Clemens W. G. M. Löwik and Laura Mezzanotte and Dominic J. Robinson},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209374},
url = {https://www.mdpi.com/1422-0067/27/20/9374},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Bremachlorin-Based Photodynamic-Therapy-Induced Effects in Low-Oxygenated Pancreatic Ductal Adenocarcinoma (PDAC) Tumor Microenvironment
AU - Roisin McMorrow
AU - Henriette S. de Bruijn
AU - Ivo Que
AU - Karishma Lila
AU - Thierry P. P. van den Bosch
AU - Michail Doukas
AU - Clemens W. G. M. Löwik
AU - Laura Mezzanotte
AU - Dominic J. Robinson
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209374
UR - https://www.mdpi.com/1422-0067/27/20/9374
AB - Photodynamic therapy (PDT) is a minimally invasive treatment whose efficacy is strongly influenced by tumor oxygenation and the tumor microenvironment (TME). Pancreatic ductal adenocarcinoma (PDAC) is characterized by severe hypoxia, dense stroma, and immune suppression, limiting therapeutic responsiveness. In this study, we investigated how Bremachlorin-based PDT remodels the TME in two murine PDAC models with distinct immune phenotypes (T-cell–high and T-cell–low) and compared them with the immunogenic MC38 colon carcinoma model. Single-fiber reflectance and fluorescence spectroscopy were used to monitor tumor physiology and photosensitizer dynamics during PDT, while multiplex immunohistochemistry enabled spatial profiling of stromal and immune components post-treatment. PDAC tumors exhibited significantly lower baseline oxygenation than MC38 tumors, which was not substantially improved by reducing the PDT fluence rate from 116 to 50 mW·cm−2. Nevertheless, PDT reduced collagen type I content in both PDAC models, indicating stromal remodeling. Importantly, illumination with a moderate fluence rate of 50 mW·cm−2 significantly increased CD8+ T-cell infiltration and improved the CD8+/neutrophil ratio in T-cell–high PDAC tumors, suggesting a shift toward a less immunosuppressive immune landscape. These findings demonstrate that Bremachlorin-PDT can modulate the PDAC tumor microenvironment and highlight the importance of immune context in shaping PDT outcomes, supporting rational optimization of PDT-based combination therapies.
SN - 1422-0067
ER -