STAT3 Pathway Targeting Type I Photosensitizer as an Immune Stimulator for Cancer Photoimmunotherapy

Abstract

Signal transducer and activator of transcription 3 (STAT3) is broadly hyperactivated in cancer cells and plays an important role in regulating cell proliferation and immunosuppression. Inhibiting STAT3 can enhance T cell-mediated antitumor immunity. Inducing immunogenic cell death (ICD) via danger-associated molecular pattern release facilitates the migration and infiltration of T cells into tumors, making ICD induction combined with STAT3 inhibition a promising synergistic cancer therapy. In this work, we discovered that an old cationic carbocyanine dye Stains-All (SA) was a STAT3 pathway targeting type I photosensitizer. SA triggered immunogenic apoptosis and pyroptosis of tumor cells and provoked antitumor immune responses. Meanwhile, SA prevented tumor growth and blocked immune escape by inhibiting STAT3 activation. Moreover, efficient ICD induction and STAT3 inhibition synergistically suppressed the growth of both primary and distant tumors. Overall, this study repurposed SA as a novel photoimmune stimulator targeting the STAT3 pathway for the synergistic tumor ablation.