Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Building 82, Room 235, 9030 Old Georgetown Road, Bethesda, MD, 20892, USA.
J Neurooncol. 2021 Jan;151(1):13-20. doi: 10.1007/s11060-020-03439-2. Epub 2020 Feb 27.
Immunotherapy, activation of the immune system to target tumor cells, represents a paradigm shift in the treatment of cancer. Immune checkpoint therapies, which target immunomodulatory molecules expressed on T-lymphocytes, have demonstrated improved survival in a variety of malignancies. However, benefit in glioblastoma, the most common and devastating malignant brain tumor, remains to be seen. With several recent clinical trials failing to show efficacy of immunotherapy, concerns have been raised regarding the impact of glucocorticoid use in this patient population that may impair the ability for immune checkpoint inhibitors to affect a response.
For this article we examined the mechanism by which immune checkpoint inhibitors activate, and glucocorticoids impair, T-lymphocyte function.
In this context, we review the clinical data of immune checkpoint inhibitors in glioblastoma as well as the impact glucocorticoids have on immune checkpoint inhibitor efficacy. Finally, we highlight key questions that remain in the field, and the potential benefit of further research for central nervous system tumors.
More information on the extent, character and duration of glucocorticoids on patients treated with PD-(L)1 will better inform both clinical management and novel therapeutic development of immunotherapy in patients with CNS malignancies.
免疫疗法，即激活免疫系统以靶向肿瘤细胞，代表了癌症治疗的范式转变。免疫检查点疗法针对 T 淋巴细胞上表达的免疫调节分子，已证明在多种恶性肿瘤中提高了生存率。然而，在胶质母细胞瘤（最常见和最具破坏性的恶性脑肿瘤）中是否能获益仍有待观察。由于最近的几项临床试验未能显示免疫疗法的疗效，人们对糖皮质激素在这类患者群体中的使用可能会影响免疫检查点抑制剂产生反应的能力产生了担忧。
本文我们研究了免疫检查点抑制剂激活以及糖皮质激素损害 T 淋巴细胞功能的机制。
在这种情况下，我们回顾了免疫检查点抑制剂在胶质母细胞瘤中的临床数据，以及糖皮质激素对免疫检查点抑制剂疗效的影响。最后，我们强调了该领域仍存在的关键问题，以及针对中枢神经系统肿瘤进一步研究的潜在获益。
更多关于接受 PD-（L）1 治疗的患者中糖皮质激素的程度、特征和持续时间的信息，将更好地为中枢神经系统恶性肿瘤患者的免疫治疗的临床管理和新的治疗方法的开发提供信息。
