Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Adv Immunol. 2012;114:217-43. doi: 10.1016/B978-0-12-396548-6.00009-3.
The induction of adaptive immunity and prevention of tolerance is a critical component of vaccination and immunotherapy in order to prevent pathogen-related diseases and to eradicate malignant cells. Although many acute infections can be controlled by vaccination, the development of prophylactic and therapeutic vaccines against persistent viruses and tumors remains challenging. The diverse immune evasion strategies used by persistent DNA viruses such as herpesviruses contribute directly to their persistence and escape from immune control. Intriguingly, many tumors have also developed escape mechanisms to dismantle similar aspects of the host's immune system. Analogous targets of immune evasion mechanisms comprise suppression of antigen presentation and T cell costimulatory pathways, induction of immunosuppressive cytokines, and obstruction of interferon and chemokine functions, which emphasizes them not only as critical elements of T cell activation pathways but also as the potential "Achilles' heels" of the host immune system. The insight that immune evasion by viruses and tumors targets analogous host immune pathways might lead to cross-pollination of the viral and tumor immunology research fields, which could lead to new perspectives and appreciation of the intricacies and subtleties that arise from the merging of these fields. Accordingly, a rational and combinatorial manipulation of immune evasion pathways and their targets should aid in the development of safer and more effective vaccine strategies and immunotherapies for a wide range of infections and malignancies.
诱导适应性免疫和预防耐受是疫苗接种和免疫治疗的一个关键组成部分，目的是预防病原体相关疾病和消灭恶性细胞。尽管许多急性感染可以通过疫苗接种来控制，但开发针对持续性病毒和肿瘤的预防性和治疗性疫苗仍然具有挑战性。持续性 DNA 病毒（如疱疹病毒）所采用的多样化免疫逃逸策略直接促成了它们的持续存在和对免疫控制的逃逸。有趣的是，许多肿瘤也已经发展出逃逸机制，以破坏宿主免疫系统的类似方面。免疫逃逸机制的类似靶标包括抑制抗原呈递和 T 细胞共刺激途径、诱导免疫抑制细胞因子以及阻断干扰素和趋化因子功能，这不仅强调了它们作为 T 细胞激活途径的关键要素，而且还强调了它们是宿主免疫系统的潜在“阿喀琉斯之踵”。病毒和肿瘤通过免疫逃逸靶向类似的宿主免疫途径这一观点可能会促成病毒学和肿瘤免疫学研究领域的交叉授粉，从而为这些领域的融合所带来的复杂性和微妙性提供新的视角和认识。因此，对免疫逃逸途径及其靶标的合理组合操作应该有助于为广泛的感染和恶性肿瘤开发更安全、更有效的疫苗策略和免疫疗法。
