Genome-wide histone acetylation underscores tumor intrinsic immune signaling induced by photothermal therapy in ovarian cancer

While the molecular signatures of ICD are well described, the epigenetic reprogramming during treatment-induced tumor intrinsic immune signaling remains unknown. Therefore, this study sought to determine the efficacy of PBNP-PTT heat shock in ovarian cancer and characterize epigenetic responses that accompany its induced tumor intrinsic immune signaling. We first demonstrate that PBNP-PTT activates tumor intrinsic immune signaling in ovarian cancer and leads to improved monocyte activation through tumor cell proinflammatory cytokine release and presentation of Calreticulin and Hsp70.

Accompanying this intrinsic immunostimulatory effect, PBNP-PTT induces genome-wide chromatin accessibility via H3K9ac, which associates with chromatin remodeling and heat shock response genes. Lastly, we show targeting histone acetylation via histone deacetylase inhibition (Panobinostat) improves the tumor intrinsic immune signaling potential of PBNP-PTT. These findings indicate that PBNP-PTT activates the release of immunostimulatory factors in ovarian cancer cells through H3K9ac rewiring and suggests the potential of combination with HDACi to improve tumor intrinsic immune signaling in ovarian cancer.