Impact of aging on cancer immunity and immunotherapy.
Impact of aging on cancer immunity and immunotherapy.
复制标题
衰老对癌症免疫力和免疫治疗的影响。
DOI：
10.1007/s00262-009-0743-2
复制
发表时间：
2009
期刊：
影响因子：
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通讯作者：
Gravekamp,Claudia
中科院分区：
文献类型：
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作者：
Pawelec,Graham;Lustgarten,Joseph;Ruby,Carl;Gravekamp,Claudia
人类癌症发病率最高的是老年人。免疫力的许多参数以一种相关的方式下降。这两种说法都是无可争议的。然而，老年人患癌症频率增加的原因是否是由于老年人免疫系统的改变，这一争议要大得多。考虑到针对自发肿瘤的免疫监视概念本身仍然存在争议，这并不奇怪。然而，某些免疫治疗方案在临床前模型中的有效性，以及在人体中获得的可重复性低得多但偶尔非常有效的治疗成功，鼓励了人们相信免疫系统可以用来控制肿瘤生长。以下“书面研讨会”的灵感来自于这样一种信念，即主动或过继免疫疗法或两者的结合将很快进入标准临床实践。鉴于大多数研究，无论是临床前研究还是临床研究，通常都是在年轻人中进行的，因此必须考虑年龄对结果的影响。最明显的是，年龄对T细胞免疫应答的影响将是非常重要的，同时也需要考虑老宿主环境对过继转移免疫效应器的有效性的影响。在这里，我们收集了一系列的论文，这些论文回顾了年龄对宿主在致癌过程中的炎症状态和免疫反应的影响。Salvioli等人讨论了百岁老人免受癌症侵害的可能原因。这可能由至少两种不同的机制介导：低igf -1介导的反应和抗炎介质的产生升高。保存良好的p53介导的反应能够阻止肿瘤发生或降低癌症侵袭性，这对百岁老人的癌症保护也至关重要。另一方面，Caruso等人讨论了检查在促进癌变中的作用。他们的结论是，只有进一步了解癌症中炎症途径的调节和功能，才能有助于理解肿瘤形成和进展的机制，并为改进新治疗方法（如药物基因组学方法）确定新的靶点。其他论文随后讨论了不同的免疫治疗模型，其中宿主的年龄和免疫系统的年龄被专门分析为影响治疗结果的变量。有大量的临床前和临床研究利用树突状细胞为基础的治疗癌症。然而，只有少数研究评估了这种类型的治疗在衰老中的效果
The highest incidence of human cancers is seen in older people. Many parameters of immunity decrease in an ageassociated manner. These two statements are each uncontroversial. However, whether the reason for the increased frequency of cancers in the elderly is due to alterations of the immune system in the old is much more controversial. Considering that the concept of immunosurveillance against spontaneously arising tumors is itself still controversial, this is hardly surprising. However, the eYcacy of certain immunotherapy protocols in preclinical models and the much less reproducible but nonetheless occasionally highly effective therapeutic successes achieved in humans encourages the belief that the immune system could be exploited to control tumor growth. The following “Symposium-in-Writing” was inspired by the belief that either active or adoptive immunotherapy or a combination of both will one day soon be entering standard clinical practice. Given that most studies, preclinical and clinical both, have most often been conducted in younger individuals, it is imperative to consider the effect of age on outcome. Most obviously, the effect of age on T cell response to vaccination will be of great importance, and also the effect of the old host environment on the eYcacy of adoptively transferred immune effectors needs consideration. Here, we have gathered a collection of papers which review the effects of age on the host in terms of inXammatory status and immune responsiveness in the carcinogenic process. Salvioli et al. discuss possible reasons why centenarians are protected from cancer. This could be mediated by at least two different mechanisms: low IGF-1-mediated responses and elevated production of anti-inXammatory mediators. A well-preserved p53-mediated response able to block tumorigenesis or to decrease cancer aggressiveness is also critical for cancer protection in centenarians. On the other hand, Caruso et al. discuss the effect that inXammation has in promoting carcinogenesis. They conclude that only further knowledge of the regulation and function of inXammatory pathways in cancer will help to understand the mechanisms of tumor formation and progression, as well as to identify new targets for the refinement of novel treatments, such as the pharmacogenomics approach. Other papers then discuss different immunotherapy models where the age of the host and the age of the immune system have been specifically analyzed as variables affecting the outcome of the treatment. There is a plethora of preclinical and clinical studies utilizing dendritic cell-based therapies for cancer. However, there are only a handful of studies evaluating the effect of this type of therapy in the aging