Tumor Microenvironment Engineering as a Strategy to Amplify Photodynamic Therapy and Immune Checkpoint Response

Photodynamic therapy (PDT) and immune checkpoint blockade (ICB) have become potentially promising tools to treat cancer, but their therapeutic effect is usually limited by the dynamic and immunosuppressing tumor core (TME). The hypoxia, thickened extra-cellular matrix, and immunosuppressive cell presence that is identified as TME, may restrict reactive oxygen species (ROS) production during PDT, and inhibit successful anti-tumor immune responses. In order to address these issues, recent discoveries in TME engineering have been aimed at programming the tumor milieu to achieve improved outcomes in either local or systemic treatments. One of them is the application of nanoparticles to deliver photosensitizer and immunomodulators into a specific region, generation and transportation of oxygen and elimination of hypoxia to increase PDT efficiency and strategies to locally activate T cells and recruit dendritic cells to potentiate immune response. Please, PDT in combination with ICB can also be used as combination therapies with synergetic action, not to mention multi-functional nanoplatforms with the ability to simultaneously regulate the TME and to administer therapeutic agents, which are shown in preclinical models. These strategies not only enhance the killing of tumor cells but also cause systemic anti-tumor immunity which may decrease recurrence and metastasis. The development of the TME is thus an established and logical approach of quelling the existing constraints of cancer treatment and gives a window to developing new ways of having more productive, safer and personalized photodynamic-immunotherapy treatments.

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