CD47 expression in Epstein-Barr virus-associated gastric carcinoma: coexistence with tumor immunity lowering the ratio of CD8+/Foxp3+ T cells
CD47 expression in Epstein-Barr virus-associated gastric carcinoma: coexistence with tumor immunity lowering the ratio of CD8+/Foxp3+ T cells
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DOI：
10.1007/s00428-018-2332-2
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发表时间：
2018-04-01
期刊：
影响因子：
3.5
通讯作者：
Fukayama, Masashi
中科院分区：
文献类型：
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作者：
Abe, Hiroyuki;Saito, Ruri;Fukayama, Masashi
Epstein-Barr病毒相关性胃癌（EBVaGC）常伴有密集的淋巴细胞浸润，提示存在与肿瘤免疫共存的特定微环境。CD47在先天免疫中介导“不要吃我”信号，在适应性抗肿瘤免疫中也很重要。我们探讨了CD47在EBVaGC与ebv阴性胃癌中的意义及其与多种免疫细胞的相关性。通过免疫组化检测，CD47在EBVaGC中高表达、低表达、阴性表达的比例分别为24%、63%、12% (n = 41)，在ebv阴性胃癌中分别为11%、49%、39% (n = 262)，说明CD47在EBVaGC中高表达频率显著增加（P = 0.043）。与ebv阴性胃癌中CD47与生存无显著相关性相比，EBVaGC中CD47高表达与较差的疾病特异性生存（P = 0.011）和总生存（P = 0.013）显著相关。为了进一步明确CD47表达在EBVaGC中的作用，免疫细胞浸润的数字图像分析显示，CD47高表达与肿瘤免疫敏感指标CD8(+)/Foxp3(+) T细胞比例较低相关（P = 0.021）。因此，CD47通过精细调节浸润T细胞的谱来降低EBVaGC的抗肿瘤免疫，这表明CD47是针对这种病毒驱动的胃癌的癌症免疫治疗的另一个靶点。
Epstein-Barr virus-associated gastric carcinoma (EBVaGC) frequently harbors dense lymphocytic infiltration, suggesting a specific microenvironment allowing coexistence with tumor immunity. CD47, which mediates the "do not eat me" signal in innate immunity, is also important in adaptive anti-tumor immunity. We investigated the significance of CD47 in EBVaGC compared with EBV-negative gastric cancer and the correlation with various immune cells. By immunohistochemistry of CD47, high, low, and negative expression was observed in 24, 63, and 12% of EBVaGC (n = 41), while 11, 49, and 39% of EBV-negative gastric cancer (n = 262), respectively, indicating that high expression of CD47 in cancer cells was significantly frequent and increased in EBVaGC (P = 0.043). In contrast to EBV-negative gastric carcinoma in which no significant correlation was observed between CD47 and survival, high expression of CD47 correlated significantly with worse disease-specific survival (P = 0.011) and overall survival (P = 0.013) in EBVaGC. To further clarify the role of CD47 expression in EBVaGC, digital image analysis of immune cell infiltration revealed that high CD47 expression was correlated with a lower ratio of CD8(+)/Foxp3(+) T cells (P = 0.021), a sensitive indicator of tumor immunity. Thus, CD47 lowers anti-tumor immunity in EBVaGC by finely tuning profile of infiltrating T cells, suggesting that CD47 is an additional target for cancer immunotherapy against this virus-driven gastric cancer.