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.

Date publication

novembre 2025

Journal

Journal of medicinal chemistry

Auteurs

Membres identifiés du Cancéropôle Est :
Dr GAIDDON Christian , Dr JUNG Alain , Dr MARTIN Sophie , Dr HARLEPP Sébastien , Dr MELLITZER Georg , Dr DETAPPE Alexandre , Dr BURGY Mickaël

Tous les auteurs :
Thibaudeau C, Bour C, Scarpi-Luttenauer M, Mesdom P, Karges J, Gandioso A, Zhou L, Harlepp S, Detappe A, Burgy M, Martin S, Mellitzer G, Gaiddon C, Gasser G, Jung AC

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/41259290

Résumé

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 ICs), 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 . Conversely, the PS that did not induce apoptotic cell death with milder stress responses resulted in a better antitumor immunity . These unexpected findings challenge the prevailing view that PDT-triggered apoptosis and ER stress are essential for ICD. Our study underscores the complexity of PDT-induced cell death balance and immunogenic signals and highlights the need to redefine ICD-inducing criteria for the rational design of next-generation PSs.

Référence

J Med Chem. 2025 11 19;: