Cyclooxygenase-2/prostaglandin E2 inhibition remodulated photodynamic therapy-associated immunosuppression for enhanced cancer immunotherapy
Low immunogenicity and immunosuppressive tumor microenvironment (TME) are two pivotal factors restricting tumor immunotherapy. Photodynamic therapy (PDT) directly destroys cancer cells by producing reactive oxygen species (ROS), and enhances the immunogenicity of ''cold'' tumors...
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Elsevier
2025-04-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425000882 |
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| author | Tao Xu Kehan Liu Shuqi Mi Yao Yao Mengyao Zhang Shujuan Xue Feng Zhi Sally-Ann Cryan Dawei Ding |
| author_facet | Tao Xu Kehan Liu Shuqi Mi Yao Yao Mengyao Zhang Shujuan Xue Feng Zhi Sally-Ann Cryan Dawei Ding |
| author_sort | Tao Xu |
| collection | DOAJ |
| description | Low immunogenicity and immunosuppressive tumor microenvironment (TME) are two pivotal factors restricting tumor immunotherapy. Photodynamic therapy (PDT) directly destroys cancer cells by producing reactive oxygen species (ROS), and enhances the immunogenicity of ''cold'' tumors by inducing immunogenic cell death (ICD), thereby promoting T cell development against tumors. However, PDT also deteriorates immunosuppression through overactivating the cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) pathway. To this end, biocompatible albumin nanoassemblies co-delivering IR780 and diclofenac are herein developed for enhanced therapy against triple-negative breast cancer. PDT-exacerbated PGE2 overexpression is effectively abolished by diclofenac-mediated COX-2 inhibition, which reprograms immunosuppressive TME via downregulating the infiltration of various immunosuppressive cells and their cytokine secretion to enhance effector T cell infiltration. Consequently, the enhanced antitumor immunity effectively inhibits tumor growth, prevents the recurrency and metastasis, and remarkably boosts the treatment efficacy of PD-L1 blockade. This study sets an intriguing example for overcoming the COX-2/PGE2 pathway-exacerbated immunosuppression alongside immune activation, thus enhancing synergistic cancer immunotherapy potentiated by various ROS-producing therapies (e.g., PDT and radiotherapy) and chemotherapy. |
| format | Article |
| id | doaj-art-79f8dd1f64f84494b72834fec3eb7b97 |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-79f8dd1f64f84494b72834fec3eb7b972025-02-06T05:12:40ZengElsevierMaterials Today Bio2590-00642025-04-0131101530Cyclooxygenase-2/prostaglandin E2 inhibition remodulated photodynamic therapy-associated immunosuppression for enhanced cancer immunotherapyTao Xu0Kehan Liu1Shuqi Mi2Yao Yao3Mengyao Zhang4Shujuan Xue5Feng Zhi6Sally-Ann Cryan7Dawei Ding8College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China; School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland (RCSI), Dublin, D02 YN77, IrelandCollege of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, ChinaCollege of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, ChinaDepartment of Gerontology, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, 223800, ChinaCollege of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, ChinaCollege of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, ChinaDepartment of Neurosurgery, The First People's Hospital of Changzhou, Changzhou, 213003, China; Clinical Medical Research Center, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China; Corresponding author. Department of Neurosurgery, The First People's Hospital of Changzhou, Changzhou, 213003, China.School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland (RCSI), Dublin, D02 YN77, Ireland; Corresponding author.College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China; Wisdom Lake Academy of Pharmacy, Xi'an Jiaotong-Liverpool University, Suzhou, 215123, China; Jiangsu Province Higher Education Key Laboratory of Cell Therapy Nanoformulation (Construction), Xi'an Jiaotong-Liverpool University, Suzhou, 215123, China; Corresponding author. Wisdom Lake Academy of Pharmacy, Xi'an Jiaotong-Liverpool University, Suzhou, 215123, China.Low immunogenicity and immunosuppressive tumor microenvironment (TME) are two pivotal factors restricting tumor immunotherapy. Photodynamic therapy (PDT) directly destroys cancer cells by producing reactive oxygen species (ROS), and enhances the immunogenicity of ''cold'' tumors by inducing immunogenic cell death (ICD), thereby promoting T cell development against tumors. However, PDT also deteriorates immunosuppression through overactivating the cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) pathway. To this end, biocompatible albumin nanoassemblies co-delivering IR780 and diclofenac are herein developed for enhanced therapy against triple-negative breast cancer. PDT-exacerbated PGE2 overexpression is effectively abolished by diclofenac-mediated COX-2 inhibition, which reprograms immunosuppressive TME via downregulating the infiltration of various immunosuppressive cells and their cytokine secretion to enhance effector T cell infiltration. Consequently, the enhanced antitumor immunity effectively inhibits tumor growth, prevents the recurrency and metastasis, and remarkably boosts the treatment efficacy of PD-L1 blockade. This study sets an intriguing example for overcoming the COX-2/PGE2 pathway-exacerbated immunosuppression alongside immune activation, thus enhancing synergistic cancer immunotherapy potentiated by various ROS-producing therapies (e.g., PDT and radiotherapy) and chemotherapy.http://www.sciencedirect.com/science/article/pii/S2590006425000882Albumin nanoparticlesPhotodynamic therapyImmunogenic cell deathCOX-2/PGE2 inhibitionImmunosuppressive tumor microenvironmentPD-L1 blockade |
| spellingShingle | Tao Xu Kehan Liu Shuqi Mi Yao Yao Mengyao Zhang Shujuan Xue Feng Zhi Sally-Ann Cryan Dawei Ding Cyclooxygenase-2/prostaglandin E2 inhibition remodulated photodynamic therapy-associated immunosuppression for enhanced cancer immunotherapy Materials Today Bio Albumin nanoparticles Photodynamic therapy Immunogenic cell death COX-2/PGE2 inhibition Immunosuppressive tumor microenvironment PD-L1 blockade |
| title | Cyclooxygenase-2/prostaglandin E2 inhibition remodulated photodynamic therapy-associated immunosuppression for enhanced cancer immunotherapy |
| title_full | Cyclooxygenase-2/prostaglandin E2 inhibition remodulated photodynamic therapy-associated immunosuppression for enhanced cancer immunotherapy |
| title_fullStr | Cyclooxygenase-2/prostaglandin E2 inhibition remodulated photodynamic therapy-associated immunosuppression for enhanced cancer immunotherapy |
| title_full_unstemmed | Cyclooxygenase-2/prostaglandin E2 inhibition remodulated photodynamic therapy-associated immunosuppression for enhanced cancer immunotherapy |
| title_short | Cyclooxygenase-2/prostaglandin E2 inhibition remodulated photodynamic therapy-associated immunosuppression for enhanced cancer immunotherapy |
| title_sort | cyclooxygenase 2 prostaglandin e2 inhibition remodulated photodynamic therapy associated immunosuppression for enhanced cancer immunotherapy |
| topic | Albumin nanoparticles Photodynamic therapy Immunogenic cell death COX-2/PGE2 inhibition Immunosuppressive tumor microenvironment PD-L1 blockade |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425000882 |
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