Tashiro Haruko, Brenner Malcolm K
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital, Texas Children's Hospital, Houston, TX 77030, USA.
Cell Res. 2017 Jan;27(1):59-73. doi: 10.1038/cr.2016.153. Epub 2016 Dec 23.
Approximately 12% of all cancers worldwide are associated with viral infections. To date, eight viruses have been shown to contribute to the development of human cancers, including Epstein-Barr virus (EBV), Hepatitis B and C viruses, and Human papilloma virus, among others. These DNA and RNA viruses produce oncogenic effects through distinct mechanisms. First, viruses may induce sustained disorders of host cell growth and survival through the genes they express, or may induce DNA damage response in host cells, which in turn increases host genome instability. Second, they may induce chronic inflammation and secondary tissue damage favoring the development of oncogenic processes in host cells. Viruses like HIV can create a more permissive environment for cancer development through immune inhibition, but we will focus on the previous two mechanisms in this review. Unlike traditional cancer therapies that cannot distinguish infected cells from non-infected cells, immunotherapies are uniquely equipped to target virus-associated malignancies. The targeting and functioning mechanisms associated with the immune response can be exploited to prevent viral infections by vaccination, and can also be used to treat infection before cancer establishment. Successes in using the immune system to eradicate established malignancy by selective recognition of virus-associated tumor cells are currently being reported. For example, numerous clinical trials of adoptive transfer of ex vivo generated virus-specific T cells have shown benefit even for established tumors in patients with EBV-associated malignancies. Additional studies in other virus-associated tumors have also been initiated and in this review we describe the current status of immunotherapy for virus-associated malignancies and discuss future prospects.
全球约12%的癌症与病毒感染有关。迄今为止，已有八种病毒被证明与人类癌症的发生有关，包括爱泼斯坦-巴尔病毒（EBV）、乙型和丙型肝炎病毒以及人乳头瘤病毒等。这些DNA和RNA病毒通过不同机制产生致癌作用。首先，病毒可能通过其表达的基因诱导宿主细胞生长和存活的持续紊乱，或者可能在宿主细胞中诱导DNA损伤反应，进而增加宿主基因组的不稳定性。其次，它们可能诱导慢性炎症和继发性组织损伤，有利于宿主细胞致癌过程的发展。像HIV这样的病毒可以通过免疫抑制为癌症发展创造更有利的环境，但在本综述中我们将重点关注前两种机制。与无法区分感染细胞和未感染细胞的传统癌症疗法不同，免疫疗法具有独特的靶向病毒相关恶性肿瘤的能力。与免疫反应相关的靶向和作用机制可用于通过疫苗接种预防病毒感染，也可用于在癌症形成前治疗感染。目前有报道称利用免疫系统通过选择性识别病毒相关肿瘤细胞来根除已形成的恶性肿瘤取得了成功。例如，大量关于体外产生的病毒特异性T细胞过继转移的临床试验表明，即使对于EBV相关恶性肿瘤患者的已形成肿瘤也有疗效。针对其他病毒相关肿瘤的更多研究也已启动，在本综述中，我们描述了病毒相关恶性肿瘤免疫治疗的现状并讨论了未来前景。
