title: Blocking the PD-1/PD-L1 pathway in glioma: a potential new treatment strategy.
abstract: Gliomas are the most common type of primary brain tumor in adults. High-grade neoplasms are associated with poor prognoses, whereas low-grade neoplasms are associated with 5-year overall survival rates of approximately 85%. Despite considerable progress in treatment modalities, the outcomes remain dismal. As is the case with many other tumors, gliomas express or secrete several immunosuppressive molecules that regulate immune cell function. Programmed death-ligand 1 (PD-L1) is a coinhibitory ligand that is predominantly expressed by tumor cells. The binding of PD-L1 to its receptor PD-1 has been demonstrated to induce an immune escape mechanism and to play a critical role in tumor initiation and development. Encouraging results following the blockade of the PD-1/PD-L1 pathway have validated PD-L1 or PD-1 as a target for cancer immunotherapy. Studies have reported that the PD-1/PD-L1 pathway plays a key role in glioma progression and in the efficacy of immunotherapies. Thus, progress in research into PD-L1 will enable us to develop a more effective and individualized immunotherapeutic strategy for gliomas. In this paper, we review PD-L1 expression, PD-L1-mediated immunosuppressive mechanisms, and the clinical applications of PD-1/PD-L1 inhibitors in gliomas. Potential treatment strategies and the challenges that may occur during the clinical development of these agents for gliomas are also reviewed.
authors.affiliation: School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, 575 Mingfu Road, Jinan, 250200, Shandong, China.|Department of Radiation Oncology and Shandong Province Key Laboratory of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, 440 Jiyan Road, Jinan, 250117, Shandong, China.
authors.forename: Song
authors.initials: S
authors.lastname: Xue
authors.affiliation: Department of Radiation Oncology and Shandong Province Key Laboratory of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, 440 Jiyan Road, Jinan, 250117, Shandong, China.|Shandong Academy of Medical Sciences, Jinan, China.
authors.forename: Man
authors.initials: M
authors.lastname: Hu
authors.affiliation: Hematology-Oncology, University of Toledo Medical Center, 1325 Conference Drive, Toledo, OH, 43614, USA.
authors.forename: Veena
authors.initials: V
authors.lastname: Iyer
authors.affiliation: Department of Radiation Oncology and Shandong Province Key Laboratory of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, 440 Jiyan Road, Jinan, 250117, Shandong, China. sdyujinming@163.com.|Shandong Academy of Medical Sciences, Jinan, China. sdyujinming@163.com.
authors.forename: Jinming
authors.initials: J
authors.lastname: Yu
mesh_terms: D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019139:Tumor Escape
chemical_list: D060890:B7-H1 Antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Expression; Glioma; Immunosuppressive; PD-1; PD-L1; Treatment