1Department of Medicine, Washington University in St. Louis, St. Louis, MO 63110 USA.
2McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO 63108 USA.
Commun Biol. 2019 Mar 22;2:109. doi: 10.1038/s42003-019-0352-3. eCollection 2019.
Viruses drive carcinogenesis in human cancers through diverse mechanisms that have not been fully elucidated but include promoting immune escape. Here we investigated associations between virus-positivity and immune pathway alteration for 2009 tumors across six virus-related cancer types. Analysis revealed that for 3 of 72 human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSC) the HPV genome integrated in immune checkpoint genes or , driving elevated expression in the corresponding gene. In addition to the previously described upregulation of the PD-1 immunosuppressive pathway in Epstein-Barr virus (EBV)-positive stomach tumors, we also observed upregulation of the PD-1 pathway in cytomegalovirus (CMV)-positive tumors. Furthermore, we found signatures of T-cell and B-cell response in HPV-positive HNSC and EBV-positive stomach tumors and HPV-positive HNSC patients were associated with better survival when T-cell signals were detected. Our work reveals that viral infection may recruit immune effector cells, and upregulate PD-1 and CTLA-4 immunosuppressive pathways.
病毒通过多种机制导致人类癌症的发生，但其具体机制尚未完全阐明，但包括促进免疫逃逸。在这里，我们研究了六种与病毒相关的癌症类型中的 2009 个肿瘤中病毒阳性与免疫途径改变之间的关联。分析显示，在 72 例人乳头瘤病毒（HPV）阳性头颈部鳞状细胞癌（HNSC）中，有 3 例 HPV 基因组整合到免疫检查点基因 或 中，导致相应基因的表达升高。除了先前描述的 EBV 阳性胃癌中 PD-1 免疫抑制途径的上调外，我们还观察到 CMV 阳性肿瘤中 PD-1 途径的上调。此外，我们在 HPV 阳性 HNSC 和 EBV 阳性胃癌中发现了 T 细胞和 B 细胞反应的特征，并且当检测到 T 细胞信号时，HPV 阳性 HNSC 患者的存活时间更长。我们的工作表明，病毒感染可能会招募免疫效应细胞，并上调 PD-1 和 CTLA-4 免疫抑制途径。
