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

J Transl Med. 2022 Nov 3;20(1):505. doi: 10.1186/s12967-022-03707-x.

Abstract

Background: 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.

Methods: 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.

Results: Immunogenic cell death (ICD) of SCC7 cells was induced by PDT with 0.5 µM of m-THPC and the 5 J/cm2 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.

Conclusion: PDT-DC vaccine enhances therapeutic effects of PD-L1 antibody, which might provide a novel approach for HNSCC immunotherapy.

Keywords: DC vaccine; Head and neck squamous cell carcinoma; Immune checkpoint; Immunotherapy; PD-L1; Photodynamic therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • B7-H1 Antigen / metabolism
  • Dendritic Cells
  • Disease Models, Animal
  • Head and Neck Neoplasms* / therapy
  • Immune Checkpoint Inhibitors*
  • Mice
  • Squamous Cell Carcinoma of Head and Neck / therapy

Substances

  • Immune Checkpoint Inhibitors
  • B7-H1 Antigen
  • Antibodies, Monoclonal