Abstract:
In CD70-expressing tumors, the interaction of CD70 on tumor cells with its lymphocyte receptor, CD27, is thought to play a role in immunosuppression in the tumor microenvironment and elevated serum levels of soluble CD27 (sCD27). Previous studies showed that CD70 is expressed in nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-related malignancy. However, the association between intratumoral CD70/CD27 expression and serum levels of sCD27 in NPC remains unclear. In the present study, we show that CD70 is primarily expressed by tumor cells in NPC and that CD27-positive lymphocytes infiltrate around tumor cells. NPC patients with CD27-positive lymphocytes had significantly better prognosis than patients lacking these cells. In addition, high CD70 expression by tumor cells tended to be correlated with shorter survival in NPC patients with CD27-positive lymphocytes. Serum sCD27 levels were significantly increased in patients with NPC and provided good diagnostic accuracy for discriminating patients from healthy individuals. The concentration of serum sCD27 in patients with CD70-positive NPC with CD27-positive lymphocytes was significantly higher than in patients with tumors negative for CD70 and/or CD27, indicating that the intratumoral CD70/CD27 interaction boosts the release of sCD27. Furthermore, positive expression of CD70 by NPC cells was significantly correlated with EBV infection. Our results suggest that CD70/CD27-targeted immunotherapies may be promising treatment options and that sCD27 may become an essential tool for evaluating the applicability of these therapies by predicting the intratumoral CD70/CD27 interaction in NPC.
摘要:
在表达CD70的肿瘤中,肿瘤细胞上CD70与其淋巴细胞受体的相互作用,CD27被认为在肿瘤微环境中的免疫抑制和可溶性CD27(sCD27)的升高的血清水平中起作用。先前的研究表明,CD70在鼻咽癌(NPC)中表达,EB病毒(EBV)相关恶性肿瘤。然而,NPC肿瘤内CD70/CD27表达与血清sCD27水平之间的关联尚不清楚.在本研究中,我们显示CD70主要由NPC中的肿瘤细胞表达,CD27阳性淋巴细胞浸润在肿瘤细胞周围。具有CD27阳性淋巴细胞的NPC患者的预后明显优于缺乏这些细胞的患者。此外,在CD27阳性淋巴细胞的NPC患者中,肿瘤细胞的CD70高表达倾向于与较短的生存期相关.NPC患者的血清sCD27水平显着升高,并为区分患者与健康个体提供了良好的诊断准确性。具有CD27阳性淋巴细胞的CD70阳性NPC患者的血清sCD27浓度明显高于CD70和/或CD27阴性的肿瘤患者,表明肿瘤内CD70/CD27相互作用促进了sCD27的释放。此外,NPC细胞CD70的阳性表达与EBV感染显著相关。我们的结果表明,CD70/CD27靶向免疫疗法可能是有前途的治疗选择,而sCD27可能成为通过预测NPC肿瘤内CD70/CD27相互作用来评估这些疗法适用性的重要工具。