title: Targeting immune checkpoints in malignant glioma.
abstract: Malignant glioma is the most common and a highly aggressive cancer in the central nervous system (CNS). Cancer immunotherapy, strategies to boost the body's anti-cancer immune responses instead of directly targeting tumor cells, recently achieved great success in treating several human solid tumors. Although once considered "immune privileged" and devoid of normal immunological functions, CNS is now considered a promising target for cancer immunotherapy, featuring the recent progresses in neurobiology and neuroimmunology and a highly immunosuppressive state in malignant glioma. In this review, we focus on immune checkpoint inhibitors, specifically, antagonizing monoclonal antibodies for programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), and indoleamine 2,3-dioxygenase (IDO). We discuss advances in the working mechanisms of these immune checkpoint molecules, their status in malignant glioma, and current preclinical and clinical trials targeting these molecules in malignant glioma.
authors.affiliation: Institute of Translational Medicine, The First Hospital, Jilin University, Changchun, China.
authors.forename: Xuhao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Translational Medicine, The First Hospital, Jilin University, Changchun, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Institute of Translational Medicine, The First Hospital, Jilin University, Changchun, China.
authors.forename: Tete
authors.initials: T
authors.lastname: Li
authors.affiliation: Institute of Translational Medicine, The First Hospital, Jilin University, Changchun, China.|Sanofi Research and Development, Cambridge, MA, USA.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.affiliation: ADC Biomedical Research Institute, Saint Paul, MN, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Institute of Translational Medicine, The First Hospital, Jilin University, Changchun, China.
authors.forename: Jingtao
authors.initials: J
authors.lastname: Chen
mesh_terms: D000074322:Antineoplastic Agents, Immunological / Q000494:pharmacology / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D002986:Clinical Trials as Topic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors
chemical_list: D000074322:Antineoplastic Agents, Immunological; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: CTLA-4; IDO; PD-1/PD-L1; immunotherapy; malignant glioma