CD47 靶向免疫疗法在 Epstein-Barr 病毒相关胃癌中释放抗肿瘤免疫。
CD47-targeted immunotherapy unleashes antitumour immunity in Epstein-Barr virus-associated gastric cancer.
机构信息
Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
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.
出版信息
Clin Immunol. 2023 Feb;247:109238. doi: 10.1016/j.clim.2023.109238. Epub 2023 Jan 20.
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.
本研究旨在增强与 Epstein-Barr 病毒相关的胃癌（EBVaGC）的抗肿瘤免疫。我们进行了 RNA-seq 分析，以比较 EBVaGC 和 EBV 阴性胃癌（EBVnGC）患者之间的差异表达基因。通过免疫组织化学分析 CD68、CD163 和 CD47 的表达水平。通过共培养模型研究了不同亚群的巨噬细胞。还检测了 CD47 阻断的效果。EBVaGC 中 CD68、CD163 和 CD47 的表达水平明显更高，与预后不良相关。与 EBV+AGS 细胞共培养的巨噬细胞倾向于免疫抑制，这可以通过 CD47 缺失或阻断 CD47 来逆转。EBV 导致 cGAS-STING 通路激活，刺激 CD47 表达并抑制巨噬细胞吞噬作用。抗 CD47 治疗激活了 cGAS-STING 信号，导致 IFN-β 的产生，从而激活抗肿瘤免疫。我们的结果为 EBVaGC 的 CD47 靶向免疫治疗提供了一种有前途的新策略。
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