Antitumor CD8 T cell responses in glioma patients are effectively suppressed by T follicular regulatory cells.

Regulatory T (Treg) cells are thought to contribute to tumor pathogenesis by suppressing tumor immunosurveillance and antitumor immunity. T follicular regulatory (Tfr) cells are a recently characterized Treg subset that expresses both the Treg transcription factor (TF) Foxp3 and the T follicular helper (Tfh) TF Bcl-6. The role of Tfr cells in glioma patients remains unclear. In this study, we found that the level of Tfr cells, identified as Foxp3+Bcl-6+ CD4 T cells, was significantly elevated in tumor-infiltrating CD4 T cells from resected glioma tumors. Both Tfr cells and Treg cells significantly suppressed the proliferation and the cytotoxic capacity of CD8 T cells toward glioma tumor cells, and the suppression was positively associated with the proportion of Tfr cells and Treg cells, respectively. Tfr and Treg cells from glioma tumor samples demonstrated higher suppression potency than those from healthy blood samples and glioma blood samples. Interestingly, canonical CXCR5- Treg cells could suppress both CXCR5+ and CXCR5- CD8 T cells, albeit with stronger potency toward CXCR5- CD8 T cells. However, Tfr cells presented much higher suppression potency toward CXCR5+ CD8 T cells, whereas CXCR5+ CD8 T cells are a potent CD8 T cell subset previously described to have antiviral and antitumor roles. Overall, these data indicate that Tfr cells are enriched in glioma tumors and have suppressive capacity toward CD8 T cell-mediated effector functions.

WBSCR22 confers cell survival and predicts poor prognosis in glioma.

Human WBSCR22 is involved in cancer proliferation, invasion and metastasis; however, its function in glioma remains unexplored. In our research, we aimed to investigate the role of WBSCR22 in the development of glioma and its possible molecular mechanisms. Using bioinformatic analysis of public datasets, we determined that WBSCR22 overexpression in glioma specimens was correlated with an unfavorable patient prognosis. Our results revealed that WBSCR22 was highly expressed in glioma cell lines. The loss of WBSCR22 inhibited the growth, invasion and migration of glioma cells, while WBSCR22 overexpression produced the opposite effects. Moreover, we found that WBSCR22 downregulation reduced the phosphorylation of Akt and GSK3ß and decreased the levels of ß-catenin and CyclinD1 in glioma cells. The opposite effects were observed when WBSCR22 was overexpressed. Additionally, we verified with a dual-luciferase reporter assay that WBSCR22 was a direct target of miR-146b-5p. Furthermore, overexpression of miR-146b-5p suppressed WBSCR22 mRNA and protein expression. Notably, the restoration of WBSCR22 expression remarkably reversed the effects of miR-146b-5p overexpression on cell survival, apoptosis and the cell cycle in glioma cells. Collectively, our findings revealed a tumor-promoting role for WBSCR22 in glioma cells, thus providing molecular evidence for WBSCR22 as a novel therapeutic target in glioma.

Using Three-Dimensional Printing to Create Individualized Cranial Nerve Models for Skull Base Tumor Surgery.

OBJECTIVE: Using three-dimensional (3D) printing to create individualized patient models of the skull base, the optic chiasm and facial nerve can be previsualized to help identify and protect these structures during tumor removal surgery. METHODS: Preoperative imaging data for 2 cases of sellar tumor and 1 case of acoustic neuroma were obtained. Based on these data, the cranial nerves were visualized using 3D T1-weighted turbo field echo sequence and diffusion tensor imaging-based fiber tracking. Mimics software was used to create 3D reconstructions of the skull base regions surrounding the tumors, and 3D solid models were printed for use in simulation of the basic surgical steps. RESULTS: The 3D printed personalized skull base tumor solid models contained information regarding the skull, brain tissue, blood vessels, cranial nerves, tumors, and other associated structures. The sphenoid sinus anatomy, saddle area, and cerebellopontine angle region could be visually displayed, and the spatial relationship between the tumor and the cranial nerves and important blood vessels was clearly defined. The models allowed for simulation of the operation, prediction of operative details, and verification of accuracy of cranial nerve reconstruction during the operation. Questionnaire assessment showed that neurosurgeons highly valued the accuracy and usefulness of these skull base tumor models. CONCLUSIONS: 3D printed models of skull base tumors and nearby cranial nerves, by allowing for the surgical procedure to be simulated beforehand, facilitate preoperative planning and help prevent cranial nerve injury.