PD-1/PD-L1 checkpoint blockades have achieved significant progress in several kinds of tumours. Pembrolizumab, which targets PD-1, has been approved as a first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with positive PD-L1 expression. However, PD-1/PD-L1 checkpoint blockades have not achieved breakthroughs in treating glioblastoma because glioblastoma has a low immunogenic response and an immunosuppressive microenvironment caused by the precise crosstalk between cytokines and immune cells. A phase III clinical trial, Checkmate 143, reported that nivolumab, which targets PD-1, did not demonstrate survival benefits compared with bavacizumab in recurrent glioblastoma patients. Thus, the combination of a PD-1/PD-L1 checkpoint blockade with RT, TMZ, antibodies targeting other inhibitory or stimulatory molecules, targeted therapy, and vaccines may be an appealing solution aimed at achieving optimal clinical benefit. There are many ongoing clinical trials exploring the efficacy of various approaches based on PD-1/PD-L1 checkpoint blockades in primary or recurrent glioblastoma patients. Many challenges need to be overcome, including the identification of discrepancies between different genomic subtypes in their response to PD-1/PD-L1 checkpoint blockades, the selection of PD-1/PD-L1 checkpoint blockades for primary versus recurrent glioblastoma, and the identification of the optimal combination and sequence of combination therapy. In this review, we describe the immunosuppressive molecular characteristics of the tumour microenvironment (TME), candidate biomarkers of PD-1/PD-L1 checkpoint blockades, ongoing clinical trials and challenges of PD-1/PD-L1 checkpoint blockades in glioblastoma.

BackgroundThe aim of this study was to summarize and discuss the similarities and differences in inflammatory biomarkers in postoperative delirium (POD) and cognitive dysfunction (POCD).MethodsA systematic retrieval of literature up to June 2017 in PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure database, and the Wanfang database was conducted. Extracted data were analyzed with STATA (version 14). The standardized mean difference (SMD) and the 95% confidence interval (95% CI) of each indicator were calculated using a random effect model. We also performed tests of heterogeneity, sensitivity analysis, assessments of bias, and meta-regression in this meta-analysis.ResultsA total of 54 observational studies were included. By meta-analysis we found significantly increased C-reactive protein (CRP) (9 studies, SMD 0.883, 95% CI 0.130 to 1.637, P = 0.022 in POD; 10 studies, SMD -0.133, 95% CI -0.512 to 0.246, P = 0.429 in POCD) and interleukin (IL)-6 (7 studies, SMD 0.386, 95% CI 0.054 to 0.717, P = 0.022 in POD; 16 studies, SMD 0.089, 95% CI -0.133 to 0.311, P = 0.433 in POCD) concentrations in both POD and POCD patients. We also found that the SMDs of CRP and IL-6 from POCD patients were positively correlated with surgery type in the meta-regression (CRP: Coefficient = 1.555365, P = 0.001, 10 studies; IL-6: Coefficient = -0.6455521, P = 0.086, 16 studies).ConclusionAvailable evidence from medium-to-high quality observational studies suggests that POD and POCD are indeed correlated with the concentration of peripheral and cerebrospinal fluid (CSF) inflammatory markers. Some of these markers, such as CRP and IL-6, play roles in both POD and POCD, while others are specific to either one of them.

IFI arm achieved better overall response and local control than ENI arm, and it allowed a dose of 68 to 74 Gy to be safely administered to patients with inoperable stage III NSCLC. Outcome improvement can be expected by conformal IFI combined with chemotherapy for stage III NSCLC.