Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Neurotherapeutics. 2017 Oct;14(4):1049-1065. doi: 10.1007/s13311-017-0513-3.
The standard of care for malignant gliomas of the brain has changed very little over the last few decades, and does not offer a cure for these rare, but fatal, tumors. The field of immunotherapy has brought potent new drugs into the oncological armamentarium, and is becoming recognized as a potentially important arm in the treatment of glioblastoma for adults. Immune checkpoints are inhibitory receptors found on immune cells that, when stimulated, cause those immune cells to become quiescent. While this is a natural mechanism to prevent excessive inflammatory damage and autoimmunity in otherwise healthy tissues, cancer cells may utilize this process to grow in the absence of targeted immune destruction. Antibodies derived to block the stimulation of these negative checkpoints, allowing immune cells to remain activated and undergo effector function, are a growing area of immunotherapy. These therapies have seen much success in both the preclinical and clinical arenas for various tumors, particularly melanoma and nonsmall-cell lung cancer. Multiple clinical trials are underway to determine if these drugs have efficacy in glioblastoma. Here, we review the current evidence, from early preclinical data to lessons learned from clinical trials outside of glioblastoma, to assess the potential of immune checkpoint inhibition in the treatment of brain tumors and discuss how this therapy may be implemented with the present standard of care.
在过去的几十年中，脑恶性胶质瘤的治疗标准变化甚微，这些罕见但致命的肿瘤仍然无法治愈。免疫疗法领域为肿瘤学武器库带来了强效的新药，并逐渐被认为是成人胶质母细胞瘤治疗的一个潜在重要手段。免疫检查点是存在于免疫细胞上的抑制性受体，当受到刺激时，会使这些免疫细胞变得静止。虽然这是一种防止在其他健康组织中发生过度炎症损伤和自身免疫的自然机制，但癌细胞可能会利用这个过程在没有靶向免疫破坏的情况下生长。为了阻断这些负性检查点的刺激，从而使免疫细胞保持激活并发挥效应功能，已经产生了许多抗体，这是免疫治疗的一个不断发展的领域。这些疗法在各种肿瘤（尤其是黑色素瘤和非小细胞肺癌）的临床前和临床领域都取得了很大的成功。目前正在进行多项临床试验，以确定这些药物在胶质母细胞瘤中的疗效。在这里，我们回顾了目前的证据，从早期的临床前数据到从胶质母细胞瘤以外的临床试验中吸取的经验教训，以评估免疫检查点抑制在治疗脑肿瘤方面的潜力，并讨论如何在目前的治疗标准下实施这种治疗方法。
