Immune-priming mechanisms of photodynamic therapy in cervical high-grade squamous intraepithelial lesions and translational implications for ovarian near-infrared photoimmunotherapy
Photodynamic therapy (PDT) offers lesion control with tissue preservation, which is important for patients seeking to avoid excision in cervical high-grade squamous intraepithelial lesions (HSIL). This review examines evidence for aminolaevulinate- and hexaminolaevulinate-based PDT as a tissue-preserving treatment for cervical HSIL and explores the biological rationale for translating near-infrared photoimmunotherapy (NIR-PIT) to intraperitoneal ovarian cancer. We summarise mechanisms by which PDT and NIR-PIT induce immunogenic cell death and engage cGAS-STING signalling, and review cervical clinical data demonstrating histologic regression, high-risk human papillomavirus clearance, and favourable tolerability. For ovarian cancer with peritoneal dissemination, we discuss how antigen-targeted NIR-PIT aligns with the immunobiology of immune-excluded serosal disease by promoting local cytotoxicity and systemic immune activation. Key translational considerations are outlined, including antigen selection, immune responsiveness, and rational combination strategies with immunomodulatory agents. Emphasis is placed on biological mechanisms and immune correlates relevant to treatment response. Overall, this review highlights the shared immunological foundations of PDT and NIR-PIT while defining distinct clinical contexts for cervical HSIL and investigational intraperitoneal ovarian cancer therapy.