2. Academic Validation
  3. CD47-targeted immunotherapy unleashes antitumour immunity in Epstein-Barr virus-associated gastric cancer

CD47-targeted immunotherapy unleashes antitumour immunity in Epstein-Barr virus-associated gastric cancer

  • Clin Immunol. 2023 Jan 20;247:109238. doi: 10.1016/j.clim.2023.109238.
Yantao Duan 1,  Shun Li 2,  Binhao Huang 1,  Yi Dou 1,  Pengfei Kong 1,  Wei Kang 3,  Dazhi Xu 4
Affiliations

Affiliations

  • 1 Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • 2 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China.
  • 3 Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong 999077, China.
  • 4 Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: xudzh@shca.org.cn.
PMID: 36690192 DOI: 10.1016/j.clim.2023.109238
Abstract

The aims of this study were to enhance the antitumour immunity in Epstein-Barr virus-associated gastric Cancer (EBVaGC). We performed RNA-seq analysis to compare the differential expression genes between EBVaGC and EBV-negative gastric Cancer (EBVnGC) patients. The expression levels of CD68, CD163 and CD47 were analyzed by immunohistochemistry. Different subsets of macrophages were investigated by a coincubation model. The effects of CD47 blockade were also detected. The expression levels of CD68, CD163 and CD47 were significantly higher in EBVaGC, and were associated with poor prognoses. Macrophages coincubated with EBV+ AGS cells tended to be immunosuppressed, which could be reversed by CD47 deficiency or blocking CD47. EBV resulted in cGAS-STING pathway activation, which stimulated CD47 expression and inhibited macrophage phagocytosis. Anti-CD47 therapy activated cGAS-STING signaling, which was responsible for production of IFN-β, resulting in activation of antitumour immunity. Our results provide a promising new strategy for CD47-targeted immunotherapy in EBVaGC.

Keywords

Antitumour immunity; CD47; EBVaGC; Immunotherapy; Macrophage; Phagocytosis.

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