BACKGROUND We sought to ascertain the immune effector function of pembrolizumab within the glioblastoma (GBM) microenvironment during the therapeutic window. METHODS In an open-label, single-center, single-arm phase II "window-of-opportunity" trial in 15 patients with recurrent (operable) GBM receiving up to 2 pembrolizumab doses before surgery and every 3 weeks afterward until disease progression or unacceptable toxicities occurred, immune responses were evaluated within the tumor. RESULTS No treatment-related deaths occurred. Overall median follow-up time was 50 months. Of 14 patients monitored, 10 had progressive disease, 3 had a partial response, and 1 had stable disease. Median progression-free survival (PFS) was 4.5 months (95% CI: 2.27, 6.83), and the 6-month PFS rate was 40%. Median overall survival (OS) was 20 months, with an estimated 1-year OS rate of 63%. GBM patients' recurrent tumors contained few T cells that demonstrated a paucity of immune activation markers, but the tumor microenvironment was markedly enriched for CD68+ macrophages. CONCLUSIONS Immune analyses indicated that pembrolizumab anti-programmed cell death 1 (PD-1) monotherapy alone can't induce effector immunologic response in most GBM patients, probably owing to a scarcity of T cells within the tumor microenvironment and a CD68+ macrophage preponderance.

中文翻译：

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pembrolizumab在复发性胶质母细胞瘤患者中的机会窗临床试验表明，免疫抑制巨噬细胞占主导地位。

背景技术我们试图确定在治疗窗期间，胶质母细胞瘤（GBM）微环境中的派姆单抗的免疫效应功能。方法在一项开放性，单中心，单组II期“机会窗”试验中，对15例复发性（可操作）GBM患者在手术前和术后每3周接受2倍派姆单抗治疗直至疾病进展或发生不可接受的毒性，在肿瘤内评估免疫反应。结果未发生与治疗有关的死亡。总体中位随访时间为50个月。在接受监测的14位患者中，有10位患有进行性疾病，3位具有部分缓解，1位患有稳定疾病。中位无进展生存期（PFS）为4.5个月（95％CI：2.27、6.83），而6个月PFS率为40％。中位总生存期（OS）为20个月，估计一年的OS率为63％。GBM患者的复发性肿瘤仅含有少量T细胞，这些免疫细胞缺乏免疫激活标记物，但肿瘤微环境中CD68 +巨噬细胞明显富集。结论免疫分析表明，在大多数GBM患者中，单独使用pembrolizumab抗程序性细胞死亡1（PD-1）单一疗法不能诱导效应免疫反应，这可能是由于肿瘤微环境中T细胞的缺乏和CD68 +巨噬细胞的优势。