Glioblastoma multiforme (GBM) is the most common and aggressive malignant tumor found in the central nervous system. Currently, standard treatments in the clinic include maximal safe surgical resection, radiation, and chemotherapy and are mostly limited by low therapeutic efficiency correlated with poor prognosis. Immunotherapy, which predominantly focuses on peptide vaccines, dendritic cell vaccines, chimeric antigen receptor T cells, checkpoint inhibitor therapy, and oncolytic virotherapy, have achieved some promising results in both preclinical and clinical trials. The future of immune therapy for GBM requires an integrated effort with rational combinations of vaccine therapy, cell therapy, and radio- and chemotherapy as well as molecule therapy targeting the tumor microenvironment.

There has been no significant improvements for immune checkpoint inhibitors since its first use. Tumour-associated macrophages (TAMs) are critical mediators in the PD-1/PD-L1 axis, contributing to the immunosuppressive tumour microenvironment. This study aims to investigate the potential role of PD-L1 in regulating TAMs in glioblastoma. Gene expression data and clinical information of glioma patients were collected from TCGA (n = 614) and CGGA (n = 325) databases. Differentially expressed genes between PD-L1high and PD-L1low groups were identified and subjected to bioinformatical analysis. We found that PD-L1 was frequently expressed in gliomas with a grade-dependent pattern. Higher PD-L1 expression predicted shorter overall survival. Moreover, PD-L1 was positively correlated with immunosuppressive cells (macrophage, neutrophil and immature DC) and negatively correlated with cytocidal immune cells (CD8+ T cell and Th1). Importantly, PD-L1 high expression was significantly correlated with M2-polarization of macrophages (M2-TAMs). We conclude that PD-L1 is an unfavourable prognostic marker for patients with glioblastoma; PD-L1-mediated immunosuppression may attribute to the infiltration and M2-polarization of TAMs.

BackgroundLower-grade gliomas (LGGs) have more favorable outcomes than glioblastomas; however, LGGs often progress to process glioblastomas within a few years. Numerous studies have proven that the tumor microenvironment (TME) is correlated with the prognosis of glioma.MethodsLGG RNA-Sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) were extracted and then divided into training and testing cohorts, respectively. Immune-related differentially expressed genes (DEGs) were screened to establish a prognostic signature by a multivariate Cox proportional hazards regression model. The immune-related risk score and clinical information, such as age, sex, World Health Organization (WHO) grade, and isocitrate dehydrogenase 1 (IDH1) mutation, were used to independently validate and develop a prognostic nomogram. GO and KEGG pathway analyses to DEGs between immune-related high-risk and low-risk groups were performed.ResultsSixteen immune-related genes were screened for establishing a prognostic signature. The risk score had a negative correlation with prognosis, with an area under the receiver operating characteristic (ROC) curve of 0.941. The risk score, age, grade, and IDH1 mutation were identified as independent prognostic factors in patients with LGGs. The hazard ratios (HRs) of the high-risk score were 5.247 [95% confidence interval (CI) = 3.060–8.996] in the multivariate analysis. A prognostic nomogram of 1-, 3-, and 5-year survival was established and validated internally and externally. Go and KEGG pathway analyses implied that immune-related biological function and pathways were involved in the TME.ConclusionThe immune-related prognostic signature and the prognostic nomogram could accurately predict survival.

Polymersomes possess the self-assembly vesicular structure similar to liposomes. Although a variety of comparisons between polymersomes and liposomes in the aspects of physical properties, preparation and applications have been elaborated in many studies, few focus on their differences in drug encapsulation, delivery and release in vitro and in vivo. In the present work, we have provided a modified direct hydration method to encapsulate anti-cancer drug paclitaxel (PTX) into PEG- b -PCL constituted polymersomes (PTX@PS). In addition to advantages including narrow particle size distribution, high colloid stability and moderate drug-loading efficiency, we find that the loaded drug aggregate in small clusters and reside through the polymersome membrane, representing a unique core-satellite structure which might facilitate the sustained drug release. Compared with commercial liposomal PTX formulation (Lipusu ® ), PTX@PS exhibited superb tumor cell killing ability underlain by multiple pro-apoptotic mechanisms. Moreover, endocytic process of PTX@PS significantly inhibits drug transporter P-gp expression which could be largely activated by free drug diffusion. In glioma mice models, it has also confirmed that PTX@PS remarkably eradicate tumors, which renders polymersomes as a promising alternative to liposomes as drug carriers in clinic.

Background: Glioma is the most common intrinsic tumor in central nervous system and is characterized by their diffuse infiltration of the brain tissue. Insulin-like Growth Factor Binding Protein-6 (IGFBP6) was associated with the insulin-like growth factor binding and insulin-like growth factor II binding processes in many cancers. Herein, we aimed to investigate the biological functions and clinical features of IGFBP6 in gliomas. Methods: Totally, we collected 325 RNA sequencing data from CGGA dataset as training cohort, and 969 RNA sequencing data from TCGA dataset as validation cohort. The clinical and molecular characteristics analysis and gene ontology analysis of IGFBP6 were performed. All analyses and graphs were produced based on R language. Results: We found that IGFBP6 expression was significantly upregulated in GBM patients and downregulated in IDH mutant patients. Receiver Operating Characteristic (ROC) analysis revealed that IGFBP6 could be used as a biomarker to predict TCGA mesenchymal subtype. GO analysis revealed that IGFBP6 was correlated with immunological functions and inflammation activities. Meanwhile, higher expression of IGFBP6 suggested significant relationship with worse prognosis in glioma patients. Conclusions: Our findings improved the understanding of IGFBP6 in glioma, and IGFBP6 might be a potential therapeutic target for glioma patients in future clinical trials.