Simultaneous Induction of Immunogenic Pyroptosis and PD-L1 Downregulation by One Single Photosensitizer for Synergistic Cancer Photoimmunotherapy

Pyroptosis, an excellent form of immunogenic cell death
that can
effectively activate antitumor immune responses, is attracting considerable
interest as a promising approach for cancer immunotherapy. Immunogenic
pyroptosis can recruit and stimulate dendritic cells to provoke further
activation and tumor infiltration of T cells by releasing danger-associated
molecular patterns, thus improving the tumor response to PD-1/PD-L1
checkpoint blockade immunotherapy. Here, we report the discovery of
a bifunctional photosensitizer Nile Violet that can simultaneously
trigger caspase-3/GSDME-mediated immunogenic pyroptosis and PD-L1
downregulation for cancer photoimmunotherapy. It was shown that this
synergistic therapeutic strategy significantly inhibited tumor growth
by triggering a systemic antitumor immune response. This work highlights
the potential of inducing immunogenic pyroptosis and PD-L1 downregulation
for synergistic tumor ablation via a single agent.