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

被引：8

作者：

Duan, Yantao ^{[1
,2
]}

Li, Shun ^{[3
]}

Huang, Binhao ^{[1
,2
]}

Dou, Yi ^{[1
,2
]}

Kong, Pengfei ^{[1
,2
]}

Kang, Wei ^{[4
]}

Xu, Dazhi ^{[1
,2
]}

机构：

[1] Fudan Univ, Shanghai Canc Ctr, Dept Gastr Surg, Shanghai 200032, Peoples R China

[2] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China

[3] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Guangdong Key Lab Nasopharyngeal Carcinoma Diag &, Guangzhou 510060, Peoples R China

[4] Chinese Univ Hong Kong, Dept Anat & Cellular Pathol, Hong Kong 999077, Peoples R China

来源：

CLINICAL IMMUNOLOGY | 2023年 / 247卷

基金：

中国国家自然科学基金;

关键词：

CD47; Immunotherapy; Macrophage; Phagocytosis; Antitumour immunity; EBVaGC; TUMOR-ASSOCIATED MACROPHAGES; EXPRESSION; ANTIBODY; RECOGNITION; SURVIVAL; PROTEIN; TARGET; PD-L1; CELLS; CD47;

D O I：

10.1016/j.clim.2023.109238

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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-beta, resulting in activation of antitumour immunity. Our results provide a promising new strategy for CD47-targeted immunotherapy in EBVaGC.

引用

页数：11

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