Cancer, aging and immunotherapy: lessons learned from animal models
Cancer, aging and immunotherapy: lessons learned from animal models
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DOI：
10.1007/s00262-009-0677-8
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发表时间：
2009-12-01
影响因子：
5.8
通讯作者：
Lustgarten, Joseph
中科院分区：
文献类型：
--
作者：
Lustgarten, Joseph
免疫系统的老化与反应性的急剧降低以及功能失调有关。随着年龄的增长，免疫功能的这种恶化与癌症发病率的增加有关。尽管有大量报告评估免疫疗法在刺激抗肿瘤免疫反应方面的作用，但大多数研究并没有关注衰老对免疫系统的影响。我们小组和其他人的研究表明，免疫疗法可能对年轻人有效，但不一定对老年人有效。为了最佳地刺激老年人的抗肿瘤免疫应答，有必要（1）识别和理解老年免疫系统的内在缺陷，以及（2）使用密切反映癌症患者的相关模型，其中自我耐受和衰老同时存在。本文综述了老年人免疫系统中存在的影响抗肿瘤免疫应答激活的缺陷、老年人激活抗肿瘤免疫应答的策略以及利用耐受性肿瘤动物模型靶向自身肿瘤抗原优化老年人免疫干预措施。
Aging of the immune system is associated with a dramatic reduction in responsiveness as well as functional dysregulation. This deterioration of immune function with advancing age is associated with an increased incidence of cancer. Although there is a plethora of reports evaluating the effect of immunotherapy in stimulating antitumor immune responses, the majority of these studies do not pay attention to the effect aging has on the immune system. Studies from our group and others indicate that immunotherapies could be effective in the young, are not necessarily effective in the old. To optimally stimulate an antitumor immune response in the old, it is necessary to (1) identify and understand the intrinsic defects of the old immune system and (2) use relevant models that closely reflect those of cancer patients, where self-tolerance and aging are present simultaneously. The present review summarizes some defects found in the old immune system affecting the activation of antitumor immune responses, the strategies used to activate stronger antitumor immune response in the old and the use of a tolerant animal tumor model to target a self-tumor antigen for the optimization of immunotherapeutic interventions in the old.