Overcoming three-layered tumor microenvironmental barriers to photodynamic therapy-induced systemic antitumor immunity
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Photodynamic therapy (PDT) induces immunogenic cell death (ICD) through reactive oxygen species (ROS) generation, bridging localized tumor ablation with systemic antitumor immunity. However, the tumor microenvironment (TME) erects three barriers that ...
MorePhotodynamic therapy (PDT) induces immunogenic cell death (ICD) through reactive oxygen species (ROS) generation, bridging localized tumor ablation with systemic antitumor immunity. However, the tumor microenvironment (TME) erects three barriers that intercept the PDT-immune cascade at distinct levels. The biochemical barrier, defined by chronic hypoxia and elevated antioxidant defenses, restricts ROS accumulation below the ICD threshold. The physical barrier, constructed by a dense extracellular matrix and activated cancer-associated fibroblasts, confines photosensitizers to the tumor periphery and excludes effector immune cells. The immunosuppressive barrier, mediated by tumor-associated macrophages, regulatory T cells, and myeloid-derived suppressor cells, neutralizes immune activation signals even after successful ICD induction. These barriers are deeply coupled: breaching any single layer yields limited benefit when the others remain intact. This review examines how barrier-oriented PDT-immunotherapy strategies, particularly nanoplatform-enabled approaches, can relieve these three barriers and restore the PDT-immune cascade.
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Yuqing Pan, Xiangdong Xue
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DOI: https://doi.org/10.70401/bmeh.2026.0032 - July 31, 2026
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This article belongs to the Special Issue Nanomaterials for Advanced Molecular Imaging in Oncology


