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Improved antitumor immunity of chemotherapy in OSCC treatment by Gasdermin-E mediated pyroptosis

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Abstract

Oral squamous cell carcinoma (OSCC) is a malignant tumor with high mortality and poor prognosis. Many OSCC patients have low response rate to current treatments including immunotherapies largely due to the immune-suppressive tumor microenvironment (TME). Chemotherapy could induce immunogenic cell death (ICD), a type of cell death such as pyroptosis and necroptosis, which has proved to be capable to alter the immune-suppressive TME and beneficial for better anti-tumor effect. GSDME, a key protein of pyroptosis, is however often silenced in tumors due to abnormal methylation. To overcome these limitations, we utilizied methyltransferase inhibitor (decitabine, DAC) to trigger pyroptosis of tumor cells, combined with chemodrug cisplatin (DDP) and immune checkpoints inhibitors to amplify the immunotherapies outcomes. To the best of our knowledge, this is the first study of tumor suppressive effect of GSDME in OSCC. Our investigation demonstrated that stimulation of GSDME expression could improve the sensitivity of chemotherapeutics, activate inflammatory tumor cell pyroptosis and alter the tumor immune-suppressive microenvironment, providing an important perspective for clinical OSCC treatment.

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Data Availability

The data sets used and analyzed in the current study are available from the corresponding author on reasonable request. All data generated or analyzed during this study are included in this published article and its supplementary files.

Abbreviations

OSCC:

Oral squamous cell carcinoma

TME:

Tumor microenvironment

ICD:

Immunogenic cell death

DAC:

Decitabine

DDP:

Cisplatin

HNSCC:

Head and neck squamous cell carcinoma

GSDME:

Gasdermin E

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Acknowledgements

The authors thank the National Center for Protein Science at Peking University in Beijing, China, for assistance with Nikon A1R confocal microscopy photography and instruction of using flow cytometer. We thank Su Lab’s help in the cell experiments at Biomedical Pioneering Innovation Center, State Key Laboratory of Protein and Plant Gene Research, School of Life Science, Peking University. We thank for Figdraw website for the picture drawing.

Funding

This work was supported by Discipline Development Fund of School of Stomatology, Peking University.

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology; School of Materials Science and Engineering, Peking University, No.22, Zhongguancun South Avenue, Haidian District, Beijing, 100871, People’s Republic of China

    Mei Zi, Lv Shixian & Wei Shicheng

  2. Biomedical Pioneering Innovation Center (BIOPIC)State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, 100871, People’s Republic of China

    Chen Xingyu & Su Xiaodong

  3. Laboratory of Biomaterials and Regenerative Medicine, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, People’s Republic of China

    Chen Yang & Wei Shicheng

  4. No.22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, People’s Republic of China

    Wei Shicheng

Authors
  1. Mei Zi
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  2. Chen Xingyu
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  3. Chen Yang
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  4. Su Xiaodong
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  5. Lv Shixian
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Contributions

ZM: contributed to conceptualization, methodology, data analysis, writing original draft, writing, review and editing; XYC: contributed to conceptualization, methodology, data analysis; YC: contributed to data analysis; XDS: contributed to original draft review; SXL: contributed to conceptualization, funding acquisition, supervision, writing-review and editing; SCW: contributed to supervision, project administration, writing-review and editing. All authors gave final approval and agree to be accountable for all aspects of the work.

Corresponding authors

Correspondence to Lv Shixian or Wei Shicheng.

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Competing interests

The authors declare no competing interests.

Ethical Approval

This study was performed in line with the principles of the Medical Ethics Committee and Biosafety Management Committee of Peking University (Approval Number LA2019197).

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Zi, M., Xingyu, C., Yang, C. et al. Improved antitumor immunity of chemotherapy in OSCC treatment by Gasdermin-E mediated pyroptosis. Apoptosis 28, 348–361 (2023). https://doi.org/10.1007/s10495-022-01792-3

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