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

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.