Immune-checkpoint blockade and active immunotherapy for glioma.
Immune-checkpoint blockade and active immunotherapy for glioma.
复制标题
免疫检查点阻滞和神经胶质瘤的主动免疫疗法。
DOI：
10.3390/cancers5041379
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发表时间：
2013-11-01
期刊：
影响因子：
5.2
通讯作者：
Okada H
中科院分区：
文献类型：
--
作者：
Ahn BJ;Pollack IF;Okada H
癌症免疫疗法已经取得了巨大的进展，包括在恶性胶质瘤患者身上取得了令人鼓舞的结果。尽管如此，由于各种原因，包括“免疫检查点”机制的运作，大脑和其中产生的肿瘤的免疫微环境仍然被认为是不够理想的，无法产生足够的抗肿瘤免疫反应。虽然这些机制在生理条件下阻止自身免疫，但恶性肿瘤，包括脑肿瘤，积极利用这些机制逃避免疫攻击。开发旨在解除这些检查点步骤的药物是目前癌症研究中最活跃的领域之一。本文综述了近年来脑肿瘤免疫学领域的研究进展，重点介绍了免疫检查点机制和主动免疫治疗策略的研究进展。在过去的十年中，许多特异性单克隆抗体被设计用来阻断免疫检查点机制，并在其他癌症中显示出疗效，如黑色素瘤。另一方面，主动免疫治疗方法，如疫苗，已经显示出令人鼓舞的结果。我们认为，有效的免疫治疗方法的发展应该最终整合这些检查点阻断剂，以提高治疗方法的疗效。有了这些药剂，这将是该领域令人兴奋的时刻。脑肿瘤免疫疗法的最终成功不仅依赖于对大脑和脑肿瘤背后的免疫学的深入理解，还依赖于合作和团队合作，以开展新的试验，解决胶质瘤中多层次的免疫挑战。
Cancer immunotherapy has made tremendous progress, including promising results in patients with malignant gliomas. Nonetheless, the immunological microenvironment of the brain and tumors arising therein is still believed to be suboptimal for sufficient antitumor immune responses for a variety of reasons, including the operation of “immune-checkpoint” mechanisms. While these mechanisms prevent autoimmunity in physiological conditions, malignant tumors, including brain tumors, actively employ these mechanisms to evade from immunological attacks. Development of agents designed to unblock these checkpoint steps is currently one of the most active areas of cancer research. In this review, we summarize recent progresses in the field of brain tumor immunology with particular foci in the area of immune-checkpoint mechanisms and development of active immunotherapy strategies. In the last decade, a number of specific monoclonal antibodies designed to block immune-checkpoint mechanisms have been developed and show efficacy in other cancers, such as melanoma. On the other hand, active immunotherapy approaches, such as vaccines, have shown encouraging outcomes. We believe that development of effective immunotherapy approaches should ultimately integrate those checkpoint-blockade agents to enhance the efficacy of therapeutic approaches. With these agents available, it is going to be quite an exciting time in the field. The eventual success of immunotherapies for brain tumors will be dependent upon not only an in-depth understanding of immunology behind the brain and brain tumors, but also collaboration and teamwork for the development of novel trials that address multiple layers of immunological challenges in gliomas.