Wilski Nicole A, Snyder Christopher M
Department of Microbiology and Immunology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Vaccines (Basel). 2019 Jul 9;7(3):62. doi: 10.3390/vaccines7030062.
Cytomegalovirus (CMV) is a herpesvirus that establishes a persistent, but generally asymptomatic, infection in most people in the world. However, CMV drives and sustains extremely large numbers of antigen-specific T cells and is, therefore, emerging as an exciting platform for vaccines against infectious diseases and cancer. Indeed, pre-clinical data strongly suggest that CMV-based vaccines can sustain protective CD8 T cell and antibody responses. In the context of vaccines for infectious diseases, substantial pre-clinical studies have elucidated the efficacy and protective mechanisms of CMV-based vaccines, including in non-human primate models of various infections. In the context of cancer vaccines, however, much less is known and only very early studies in mice have been conducted. To develop CMV-based cancer vaccines further, it will be critical to better understand the complex interaction of CMV and cancer. An array of evidence suggests that naturally-acquired human (H)CMV can be detected in cancers, and it has been proposed that HCMV may promote tumor growth. This would obviously be a concern for any therapeutic cancer vaccines. In experimental models, CMV has been shown to play both positive and negative roles in tumor progression, depending on the model studied. However, the mechanisms are still largely unknown. Thus, more studies assessing the interaction of CMV with the tumor microenvironment are needed. This review will summarize the existing literature and major open questions about CMV-based vaccines for cancer, and discuss our hypothesis that the balance between pro-tumor and anti-tumor effects driven by CMV depends on the location and the activity of the virus in the lesion.
巨细胞病毒（CMV）是一种疱疹病毒，在世界上大多数人中会引发持续感染，但通常没有症状。然而，CMV能驱动并维持大量抗原特异性T细胞，因此正成为一种用于预防传染病和癌症的令人兴奋的疫苗平台。实际上，临床前数据有力地表明，基于CMV的疫苗能够维持具有保护性的CD8 T细胞和抗体反应。在传染病疫苗方面，大量临床前研究已经阐明了基于CMV的疫苗的功效和保护机制，包括在各种感染的非人灵长类动物模型中的研究。然而，在癌症疫苗方面，人们了解得很少，仅在小鼠中开展了非常早期的研究。为了进一步开发基于CMV的癌症疫苗，更好地理解CMV与癌症之间的复杂相互作用至关重要。一系列证据表明，在癌症中可以检测到自然获得的人巨细胞病毒（HCMV），并且有人提出HCMV可能促进肿瘤生长。这显然会是任何治疗性癌症疫苗所关注的问题。在实验模型中，根据所研究的模型，CMV在肿瘤进展中已显示出既具有积极作用也具有消极作用。然而，其机制在很大程度上仍然未知。因此，需要更多研究来评估CMV与肿瘤微环境之间相互作用。本综述将总结关于基于CMV的癌症疫苗的现有文献和主要未解决问题，并讨论我们的假设，即CMV驱动的促肿瘤和抗肿瘤作用之间的平衡取决于病毒在病变中的位置和活性。
