A photodynamically sensitized dendritic cell vaccine that promotes the anti-tumor effects of anti-PD-L1 monoclonal antibody in a murine model of head and neck squamous cell carcinoma

• Published in: Journal of translational medicine 2022-11, Vol.20 (1), p.505-505, Article 505
• Main Authors: Li, Shuang, Wang, Ding, Cheng, Jinzhang, Sun, Jicheng, Kalvakolanu, Dhan V, Zhao, Xue, Wang, Di, You, Yunhan, Zhang, Ling, Yu, Dan
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antigens; Apoptosis; B7-H1 Antigen - metabolism; Cancer; Care and treatment; Cell death; Cholecystokinin; Cytokines; DC vaccine; Dendritic Cells; Disease Models, Animal; Dosage and administration; Enzyme-linked immunosorbent assay; Evaluation; Experiments; FDA approval; Flow cytometry; Fluorescence microscopy; Head & neck cancer; Head and neck cancer; Head and neck carcinoma; Head and Neck Neoplasms - therapy; Head and neck squamous cell carcinoma; Immune checkpoint; Immune Checkpoint Inhibitors; Immunogenicity; Immunotherapy; Laboratory animals; Methods; Mice; Monoclonal antibodies; Patient outcomes; PD-L1; PD-L1 protein; Photochemotherapy; Photodynamic therapy; Phototoxicity; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - therapy; Tumors; Vaccines
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-022-03707-x

Immune checkpoint inhibitors are promising tools in combating several cancers, including head and neck squamous cell carcinoma (HNSCC). However, a substantial portion of HNSCC patients do not respond to PD-L1 antibody. Here we describe a photodynamic therapeutic (PDT) approach to enhance anti-tumor effects of the anti-PD-L1 antibody. Phototoxicity of PDT was confirmed using fluorescence microscopy, Cell Counting Kit-8 (CCK-8), Enzyme Linked Immunosorbent Assay (ELISA) and flow cytometry analyses. Phenotypic and functional maturation of immature DCs (imDCs) induced by PDT were measured using flow cytometry and ELISA. A mouse model was established using the HNSCC line, SCC7, and was used to evaluate therapeutic effects of PDT-DC vaccine in facilitating anti-tumor immunity of PD-L1 antibody. Immunogenic cell death (ICD) of SCC7 cells was induced by PDT with 0.5 µM of m-THPC and the 5 J/cm of light dose. ICD of SCC7 cells stimulated imDCs maturation. In vivo assays suggested that PDT-DC vaccine and anti-PD-L1 mAb synergistically induced anti-tumor immunity and suppressed tumor progression. PDT-DC vaccine enhances therapeutic effects of PD-L1 antibody, which might provide a novel approach for HNSCC immunotherapy.