Iridium(III)-Based PD-L1 Agonist Regulates p62 and ATF3 for Enhanced Cancer Immunotherapy

Anti-PD-L1
immunotherapy, a new lung cancer treatment,
is limited
to a few patients due to low PD-L1 expression and tumor immunosuppression.
To address these challenges, the upregulation of PD-L1 has the potential
to elevate the response rate and efficiency of anti-PD-L1 and alleviate
the immunosuppression of the tumor microenvironment. Herein, we developed
a novel usnic acid-derived Iridium(III) complex, Ir-UA, that boosts PD-L1 expression and converts “cold tumors”
to “hot”. Subsequently, we administered Ir-UA combined with anti-PD-L1 in mice, which effectively inhibited tumor
growth and promoted CD4+ and CD8+ T cell infiltration.
To our knowledge, Ir-UA is the first iridium-based complex
to stimulate the expression of PD-L1 by explicitly regulating its
transcription factors, which not only provides a promising platform
for immune checkpoint blockade but, more importantly, provides an
effective treatment strategy for patients with low PD-L1 expression.