Related Experiment Video

Updated: Jan 8, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
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An EBNA1-YAP signaling axis drives immune escape through CD276 in EBV-associated gastric cancer

Binhao Huang1,2, Mengqi Liu1,3, Yantao Duan1,2

  • 1Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.

Cell Death & Disease
|December 19, 2025
PubMed

Insights

Researchers identified CD276 as a key molecule driving immune evasion in Epstein-Barr virus-associated gastric cancer (EBVaGC). Targeting CD276 alongside PD1 blockade shows promise for improving anti-tumor immunity in EBVaGC patients.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Epstein-Barr virus-associated gastric cancer (EBVaGC) shows limited response to anti-PD1 immunotherapy.
  • Understanding immune escape mechanisms is crucial for developing effective cancer treatments.

Purpose of the Study:

  • To identify novel immune checkpoint molecules involved in EBVaGC immune escape.
  • To elucidate the mechanism of CD276-mediated immunosuppression in EBVaGC.
  • To evaluate CD276 as a therapeutic target in combination with PD1 blockade.

Main Methods:

  • Immune checkpoint screening using transcriptome profiling and immunohistochemistry.
  • In vitro and in vivo experiments to assess CD276 function.
  • Mechanism studies involving YAP/TEAD4 signaling and EBNA1.
  • Evaluation of combination therapy in a humanized xenograft mouse model.

Main Results:

  • CD276 was identified as an independent immunosuppressive molecule correlating with poor EBVaGC prognosis.
  • CD276 induces T cell apoptosis and reduces chemokine secretion, hindering anti-tumor immunity.
  • The EBNA1-YAP-CD276 axis drives CD276 upregulation in EBVaGC.
  • Combined CD276 and PD1 blockade significantly reduced tumor size in a preclinical model.

Conclusions:

  • The EBNA1-YAP-CD276 axis represents a novel mechanism of immune escape in EBVaGC.
  • CD276 is a potential therapeutic target to overcome resistance to anti-PD1 immunotherapy in EBVaGC.
  • Targeting CD276 offers a promising strategy for enhancing anti-tumor immunity in EBVaGC.

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