Viral Immunobiology Department, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
J Med Virol. 2023 Jan;95(1):e27840. doi: 10.1002/jmv.27840. Epub 2022 May 17.
Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) are two persistent oncogenic γ-herpesviruses with an exclusive tropism for humans. They cause cancers of lymphocyte, epithelial and endothelial cell origin, such as Burkitt's and Hodgkin's lymphoma, primary effusion lymphoma, nasopharyngeal carcinoma, and Kaposi sarcoma. Mutations in immune-related genes but also adverse events during immune checkpoint inhibition in cancer patients have revealed molecular requirements for immune control of EBV and KSHV. These include costimulatory and coinhibitory receptors on T cells that are currently explored or already therapeutically targeted in tumor patients. This review discusses these co-receptors and their influence on EBV- and KSHV-associated diseases. The respective studies reveal surprising specificities of some of these receptors for immunity to these tumor viruses, benefits of their blockade for some but not other virus-associated diseases, and that EBV- and KSHV-specific immune control should be monitored during immune checkpoint inhibition to prevent adverse events that might be associated with their reactivation during treatment.
爱泼斯坦-巴尔病毒（EBV）和卡波西肉瘤相关疱疹病毒（KSHV）是两种具有独特嗜人性的潜伏性致癌γ疱疹病毒。它们可引起淋巴细胞、上皮细胞和内皮细胞来源的癌症，如伯基特淋巴瘤和霍奇金淋巴瘤、原发性渗出性淋巴瘤、鼻咽癌和卡波西肉瘤。免疫相关基因的突变以及癌症患者免疫检查点抑制过程中的不良事件，揭示了 EBV 和 KSHV 免疫控制的分子要求。这些包括 T 细胞上的共刺激和共抑制受体，目前正在肿瘤患者中进行探索或已经作为治疗靶点。本文讨论了这些共受体及其对 EBV 和 KSHV 相关疾病的影响。各自的研究揭示了这些受体中一些对于这些肿瘤病毒的免疫具有惊人的特异性，其阻断对某些但不是其他病毒相关疾病有益，并且在免疫检查点抑制期间应监测 EBV 和 KSHV 特异性免疫控制，以预防与治疗期间病毒重新激活相关的不良事件。
