Photodynamic-Immunotherapy Synergy: Decoding the Spatiotemporal Regulation of Tumour Immunogenicity for Enhanced PD-1 Blockade.

In recent years, breakthrough advancements have been achieved in cancer immunotherapy, particularly through immune checkpoint inhibition targeting the PD-1/PD-L1 pathway. This approach reverses the immunosuppressive effect of tumour cells on T lymphocytes, thereby reinstating antitumour immune responses and demonstrating considerable clinical efficacy. Photodynamic therapy (PDT), which operates via a unique localised mechanism, not only induces direct tumour cell ablation by generating reactive oxygen species (ROS) through photosensitizers, but also promotes immunogenic cell death (ICD), leading to the activation of systemic antitumour immunity. Growing evidence indicates that the combination of PD-1 blockade and PDT produces cooperative effects within the tumour microenvironment, amplifying immune activation. Such a strategy alleviates T-cell immunosuppression post-PDT, thereby forming a positive feedback loop that improves therapeutic performance. This review summarises the mechanistic rationale underlying the combined application of PDT and anti-PD-1 therapy, with emphasis on their synergistic interplay in the tumour microenvironment, as well as recent advances in nanomaterial-based strategies aimed at resolving hypoxia-related limitations and enhancing targeting precision. Furthermore, current challenges and future directions for this combinatorial regimen are discussed.