Target Immune Checkpoint Molecules in Trasgenic HNSCC Mouse Model

Objectives: Immunotherapy with immune checkpoint molecule specific monoclonal antibody have obtained encouraging results from preclinical studies and clinical trials, which promoted us to explore whether this kind of immunotherapy could be applicable to head and neck squamous cell carcinoma (HNSCC). This report summarized our published and unpublished studies on immune checkpoint molecule eg. PD1, CTLA4, LAG3, TIM3, B7-H4 and VISTA.
Methods: Expression and correlation of these molecules were carried out in 165 primary human HNSCC tissues.
Results: Survival analysis reveals B7-H4, LAG3 and CTLA4/CD8 ratio may have potential prognostic means. Study in immunocompetent genetically defined HNSCC mouse model by conditional deletion Tgfbr1/Pten in oral mucosa reports that target immune checkpoint molecules using in vivo monoclone antibody may have therapeutic potential in mice HNSCC. Flow cytometry analysis reveals target immune checkpoint molecules may decrease CD11b+Gr1+ myeloid-derived suppressor cells (MDSCs), CD4+Foxp3+ regulatory T cells (Tregs) or CD11b+F4/80+ tumor associated macrophages (TAMs).
Conclusions: Collectively, our results offer a preclinical rationale supporting the immunomodulatory effects of immune checkpoint molecules and suggest a potential therapeutic target of immunotherapy for HNSCC.