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.

T lymphocyte-targeted immune checkpoint modulation in glioma

“…61 Estimates of PD-L1 expression on human GBM have ranged between 19% and 88%, with some variation ascribed to the technique and antibody use. [62][63][64] Prognostically, PD-1 expression on TILS and PD-L1 expression on tumor cells Open access both correlate with glioma grade. 65 Zeng et al, described improved survival in murine models with the combination of PD-1 inhibitor plus radiotherapy.…”

Large-scale analysis reveals the specific clinical and immune features of B7-H3 in glioma

“…26 Recently, remarkable progress has been made in the clinical trial of immune checkpoint inhibitors targeting B7-CD28 family members in glioma, lighting up the bright future of glioma treatment. 27,28 B7-H3 is a member of the B7 family and shows great potential for cancer immunotherapy. More importantly, compared to other B7 and CD28 family members in glioma, B7-H3 showed a significant higher expression, indicating that targeting B7-H3 may have a better affinity.…”

Semimechanistically Based Modeling of Pembrolizumab Time-Varying Clearance Using 4 Longitudinal Covariates in Patients With Non–Small Cell Lung Cancer

“…1 Monoclonal antibodies (mAbs) targeting programmed death-1 ligands (PD-L1 and PD-L2) have been showing noticeable clinical benefits as monotherapy or in combination with other anticancer agents. [2][3][4][5][6] PD-L1 mAbs have been approved for treating patients with melanoma, nonesmall cell lung cancer (NSCLC), renal cell carcinoma, urothelial cancer, head and neck squamous cell carcinoma, non-Hodgkins lymphoma, gastric cancer, microsatellite instabilityehigh patients regardless of tumor type, and so forth. Particularly, the approval of pembrolizumab as the first-line NSCLC therapy suggested that immunotherapy may become a new standard of care in advanced NSCLC, which is a major global mortality reason.…”