Synergization of an endoplasmic reticulum-targeted iridium(III) photosensitizer with PD-L1 inhibitor for oral squamous cell carcinoma immunotherapy

Inefficient activation of tumor immunogenicity and sustained immunosuppressive microenvironments severely impede the clinical application of photodynamic therapy (PDT) in oral squamous cell carcinoma (OSCC). Herein, two type I/II iridium(III) photosensitizers (Ir1 and Ir2) targeting endoplasmic reticulum (ER) are designed as immunogenic cell death (ICD) inducers. Ir1-meidated PDT treatment adaptively upregulates the programmed death-ligand 1 (PD-L1) expression in vitro. Moreover, Ir1-mediated PDT stimulates dendritic cell maturation, T lymphocyte infiltration and antitumor cytokine secretion, and synergizes with PD-L1 inhibitor to transform immune-suppressive "cold tumor" to immune-responsive "hot tumor" in vivo. Our study firstly paves the way for the combination of metal-based photosensitizing ICD inducer with PD-L1 inhibitor for enhanced immunotherapy.