Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages

被引：132

作者：

de Groot, John ^{[1
]}

Penas-Prado, Marta ^{[1
]}

Alfaro-Munoz, Kristin ^{[1
]}

Hunter, Kathy ^{[1
]}

Pei, Be Lian ^{[1
]}

O'Brien, Barbara ^{[1
]}

Weathers, Shiao-Pei ^{[1
]}

Loghin, Monica ^{[1
]}

Kamiya Matsouka, Carlos ^{[1
]}

Yung, W. K. Alfred ^{[1
]}

Mandel, Jacob ^{[6
]}

Wu, Jimin ^{[2
]}

Yuan, Ying ^{[2
]}

Zhou, Shouhao ^{[2
]}

Fuller, Gregory N. ^{[3
]}

Huse, Jason ^{[3
]}

Rao, Ganesh ^{[4
]}

Weinberg, Jeffrey S. ^{[4
]}

Prabhu, Sujit S. ^{[4
]}

McCutcheon, Ian E. ^{[4
]}

Lang, Frederick F. ^{[4
]}

Ferguson, Sherise D. ^{[4
]}

Sawaya, Raymond ^{[4
]}

Colen, Rivka ^{[5
]}

Yadav, Shalini S. ^{[5
]}

Blando, Jorge ^{[5
]}

Vence, Luis ^{[5
]}

Allison, James ^{[5
]}

Sharma, Padmanee ^{[5
]}

Heimberger, Amy B. ^{[4
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Neuropathol, Houston, TX 77030 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, 1400 Holcombe Blvd, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Canc Syst Imaging, Houston, TX 77030 USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA

来源：

NEURO-ONCOLOGY | 2020年 / 22卷 / 04期

关键词：

pembrolizumab; glioblastoma multiforme; immune suppression; macrophages; clinical trial; PROGNOSTIC IMPACT; PD-L1; EXPRESSION; GLIOMA; CELLS; INHIBITION; RESISTANCE; SIGNATURES; ANTI-PD-1; THERAPY;

D O I：

10.1093/neuonc/noz185

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：539 / 549

页数：11

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