IADR Abstract Archives
Programming Cell Pyroptosis Using Biomaterials for OSCC Immunotherapy
Objectives: Programmed cell deaths (PCD) have played crucial role in tumor cell death. As a representative, pyroptosis is a lytic form of programmed death initiated by inflammasomes, associated with adaptive immune responses. Our objective is to design an adhesion chitosan hydrogel that trigger oral squamous cell carcinoma (OSCC) tumor cell pyroptosis via epigenetics and further enhances the immune effects of chemotherapy
Methods: In the 4-nitroquinoline N-oxide (4-NQO)-induced murine OSCC model, epigenetic inhibitor decitabine(DAC) was pre-treated to achieve the demethylation of GSDME in tumor cells. Subsequently, constructed an adhesive chitosan hydrogel and applied to the surface of OSCC to activate the GSDME/ Caspase-3 pathway and immune system of tumor cells and trigger cell pyroptosis.
Results: Low-dose methyltransferase inhibitor DAC can significantly up-regulate GSDME expression in tumor cells by demethylation. In vitro and in vivo experiments have demonstrated that chemotherapeutic agents can reverse the silencing of GSDME by DAC sensitized tumor cells, induce pyroptosis and improve the chemotherapeutic efficacy and immune response of OSCC.
Conclusions: According to the results of its antitumor activity, anti-metastasis and inhibition of recurrence, this pyroptosis-based chemotherapy strategy improves the immune effect of chemotherapy and provides important insights into cancer immunotherapy
Methods: In the 4-nitroquinoline N-oxide (4-NQO)-induced murine OSCC model, epigenetic inhibitor decitabine(DAC) was pre-treated to achieve the demethylation of GSDME in tumor cells. Subsequently, constructed an adhesive chitosan hydrogel and applied to the surface of OSCC to activate the GSDME/ Caspase-3 pathway and immune system of tumor cells and trigger cell pyroptosis.
Results: Low-dose methyltransferase inhibitor DAC can significantly up-regulate GSDME expression in tumor cells by demethylation. In vitro and in vivo experiments have demonstrated that chemotherapeutic agents can reverse the silencing of GSDME by DAC sensitized tumor cells, induce pyroptosis and improve the chemotherapeutic efficacy and immune response of OSCC.
Conclusions: According to the results of its antitumor activity, anti-metastasis and inhibition of recurrence, this pyroptosis-based chemotherapy strategy improves the immune effect of chemotherapy and provides important insights into cancer immunotherapy