Immune Checkpoint in Glioblastoma: Promising and Challenging

Abstract

Glioblastoma (GBM) is a severe malignant brain cancer with poor overall survival. Conventional intervention remains dismal to prevent recurrence and deterioration of GBM cell. Recent years have witnessed exciting breakthroughs in novel immune strategies, especially checkpoint inhibitors, some of which have become adjuvant setting after standard of care in melanoma. Several clinical trials of checkpoint inhibitors are ongoing in glioblastoma and other brain carcinomas. Plus, synergistic combinations of checkpoint inhibitors with conventional therapy strategies—radiotherapy, temozolomide, bevacizumab, and corticosteroids are now being exploited and applied in clinical settings. This review highlights the recent developments of checkpoints in GBM immunotherapy to provide a brief and comprehensive review of current treatment options. Furthermore, we will discuss challenges remained, such as unique immune system of central nervous system (CNS), immune-related toxicities, synergies, and adverse interactions of combination therapies.

High expression of COPB2 predicts adverse outcomes: A potential therapeutic target for glioma

“…In recent years, the use of immune checkpoint inhibitors (ICIs) has been popular in the treatment of malignant tumors . Some ICIs, such as anti‐ PD‐1 antibody, are superior to traditional chemoradiotherapy in terms of its clinical curative effect . However, certain types of malignant tumors, such as glioblastoma, are resistant to monotherapy with ICIs .…”

“…Some ICIs, such as anti‐ PD‐1 antibody, are superior to traditional chemoradiotherapy in terms of its clinical curative effect . However, certain types of malignant tumors, such as glioblastoma, are resistant to monotherapy with ICIs . Therefore, new immunotherapeutic targets are urgently needed to treat glioma.…”

“…25,26 Some ICIs, such as anti-PD-1 antibody, are superior to traditional chemoradiotherapy in terms of its clinical curative effect. 27…”

Nivolumab maintenance after salvage autologous stem cell transplantation results in long‐term remission in multiple relapsed primary CNS lymphoma

“…Activated and check point inhibitor reinvigorated T cells may then reach CNS via lymphatic vessels. 9 Johanns et al 8 reported an increased lymphocyte infiltration and radiographic response in a glioblastoma with mutator phenotype subsequent to pembrolizumab application. This is suggestive of active CNS immune response following checkpoint blockade therapy.…”

Unconventional Approaches to Modulating the Immunogenicity of Tumor Cells

“…And, several pan-HDAC inhibitors, such as sodium valproate, etinostat, panobinostat, and vorinostat, have all been shown in vivo to enhance the antitumor efficacy of checkpoint inhibitory antibodies, as well as promote activated T cell infiltration into the tumors (Booth, Roberts, Poklepovic, & Dent, 2017; Booth, Roberts, Poklepovic, Kirkwood, & Dent, 2017; Christiansen et al, 2011; Gameiro, Malamas, Tsang, Ferrone, & Hodge, 2016; Hornig, Heppt, Graf, Ruzicka, & Berking, 2016; Kroesen et al, 2016; Vo et al, 2009; West & Johnstone, 2014; West et al, 2013). Tumor types tested in these studies are diverse and include melanoma, breast, colorectal, glioblastoma, and hepatoma (Chae, Wang, Nimeiri, Kalyan, & Giles, 2017; Huang et al, 2017; Keller, Zhang, Li, Schaider, & Wells, 2017; Monnot & Romero, 2017; Rai et al, 2017). …”