2. Academic Validation
  3. Dehydroepiandrosterone attenuated the immune escape of oral squamous cell carcinoma through NF-κB p65/miR-15b-5p/B7-H4 axis

Dehydroepiandrosterone attenuated the immune escape of oral squamous cell carcinoma through NF-κB p65/miR-15b-5p/B7-H4 axis

  • Int Immunopharmacol. 2024 Jun 16:137:112480. doi: 10.1016/j.intimp.2024.112480.
Yifei Wang 1,  Ruiliu Li 2,  Ruoshui Yuan 2,  Lin Wang 2,  Qiao Qiao 2,  Zhenyuan Han 2,  Qingxiang Li 2,  Yuke Li 2,  Yuxing Guo 2,  Chuanbin Guo 3
Affiliations

Affiliations

  • 1 Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, PR China. Electronic address: wyf_pkuss@126.com.
  • 2 Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, PR China.
  • 3 Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, No. 22, Zhongguancun South Avenue, Haidian District, Beijing 100081, PR China. Electronic address: guodazuo@sina.com.
PMID: 38885603 DOI: 10.1016/j.intimp.2024.112480
Abstract

Objectives: We aimed to explore the effects and mechanisms of action of dehydroepiandrosterone (DHEA) on immune evasion of oral squamous cell carcinoma (OSCC) to provide evidence for enhancing the effect of immunotherapy.

Materials and methods: A xenograft mouse model and immunohistochemistry were used to reveal the patterns of tumor-infiltrating lymphocytes (TILs). The CAL27 and SCC VII cell lines were used for the in vitro study. Western blotting, qPCR, immunofluorescence, and flow cytometry were used to evaluate the expression of B7-H4. Recombinant mouse B7-H4 protein (rmB7-H4) and PG490, an inhibitor of NF-κB p65 were used for the "rescue study." Gain- and loss-of-function, luciferase reporter, and chromatin immunoprecipitation assays were performed to verify this mechanism.

Results: DHEA inhibited tumor growth in an OSCC xenograft mouse model, increased CD8 + cells, and decreased FOXP3 + cells in TILs. DHEA reduced the expression of B7-H4 in CAL27 and SCC VII cells RmB7-H4 reverses the effect of DHEA on tumor growth and TIL patterns. DHEA increased the expression of miR-15b-5p and activated its transcriptional factor NF-κB p65. Further experiments demonstrated that miR-15b-5p inhibited B7-H4 expression by binding to its 3'-UTR regions, and NF-κB p65 activated miR-15b transcription. PG490 reversed the effects of DHEA on tumor growth, antitumor immunity in the OSCC xenograft model, and the expression/phosphorylation of NF-κB p65, miR-15b-5p, and B7-H4.

Conclusions: This study indicates that DHEA attenuates the immune escape of OSCC cells by inhibiting B7-H4 expression, providing new insights for Cancer Immunotherapy.

Keywords

B7-H4; Dehydroepiandrosterone; NF-κB; Oral squamous cell carcinoma; Tumor-infiltrating lymphocyte.

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