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

John De Groot, Marta Penas-Prado, Kristin Alfaro-Munoz, Kathy Hunter, Be Lian Pei, Barbara O'Brien, Shiao Pei Weathers, Monica Loghin, Carlos Kamiya Matsouka, W. K.Alfred Yung, Jacob Mandel, Jimin Wu, Ying Yuan, Shouhao Zhou, Gregory N. Fuller, Jason Huse, Ganesh Rao, Jeffrey S. Weinberg, Sujit S. Prabhu, Ian E. McCutcheonFrederick F. Lang, Sherise D. Ferguson, Raymond Sawaya, Rivka Colen, Shalini S. Yadav, Jorge Blando, Luis Vence, James Allison, Padmanee Sharma, Amy B. Heimberger

Research output: Contribution to journalArticlepeer-review

91 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)539-549
Number of pages11
Issue number4
StatePublished - Apr 15 2020

All Science Journal Classification (ASJC) codes

  • Oncology
  • Clinical Neurology
  • Cancer Research


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