Inverse Correlation between Endoplasmic Reticulum Stress Intensity and Antitumor Immune Response with Ruthenium(II)-Based Photosensitizers for the Photodynamic Therapy of Head and Neck Squamous Cell Carcinoma.

ABSTRACT: Photodynamic therapy (PDT) is a promising strategy for head and neck squamous cell carcinoma (HNSCC), but the immune consequences of tumor cell death remain incompletely understood. We compared two ruthenium(II) polypyridine photosensitizers (PSs) in HNSCC models and found that both were potently phototoxic (nanomolar IC₅₀s), triggered diverse cell death pathways (including autophagy and ferroptosis), and promoted hallmark danger signals of immunogenic cell death (ICD). Strikingly, only one PS induced apoptosis and strong endoplasmic reticulum (ER) stress, yet paradoxically led to immune tolerance in vivo. Conversely, the PS that did not induce apoptotic cell death with milder stress responses resulted in a better antitumor immunity in vivo. These unexpected findin

SUBMITTER: Thibaudeau C 

PROVIDER: S-EPMC12703731 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature