The role of the dura mater in cerebral metastases.

OBJECTIVE: The objective of this review was to describe the immunological changes that take place in the dura mater in response to metastatic disease that seeds the CNS. The authors hypothesized that the dura's anatomy and resident immune cell population play a role in enabling metastasis to the brain and leptomeninges. METHODS: An extensive literature search was conducted to identify evidence that supports the dura's participation in metastasis to the CNS. The authors' hypothesis was informed by a recent upsurge in studies that have investigated the dura's role in metastatic development, CNS infections, and autoimmunity. They reviewed this literature as well as the use of immunotherapy in treating brain metastases and how these therapies change the meningeal immune landscape to overcome and reverse tumor-promoting immunosuppression. RESULTS: Evidence suggests that the unique architecture and immune cell profile of the dura, compared with other immune compartments within the CNS, facilitate entry of metastatic tumor cells into the brain. Once these tumor cells penetrate the dural barrier, they propagate an immunosuppressive tumor microenvironment. Therefore, immunotherapy may serve to overcome this immunosuppressive environment and liberate proinflammatory immune cells in an effort to combat metastatic disease. CONCLUSIONS: Within the next few years, the authors expect the addition of several more scientific studies into the literature that further underscore the dura as a chief participant and neuroanatomical barrier in neuro-oncology.

Dural Closure Techniques and Cerebrospinal Fluid Leak Incidence After Resection of Primary Intradural Spinal Tumors: A Systematic Review.

STUDY DESIGN: This is a systematic review of primary intradural spinal tumors (PIDSTs) and the frequency of postoperative cerebrospinal fluid (CSF) leaks. OBJECTIVE: This study aimed to compare CSF leak rates among techniques for dural watertight closure (WTC) after the resection of PIDSTs. SUMMARY OF BACKGROUND DATA: Resection of PIDSTs may result in persistent CSF leak. This complication is associated with infection, wound dehiscence, increased length of stay, and morbidity. Dural closure techniques have been developed to decrease the CSF leak rate. METHODS: A PubMed search was performed in 2022 with these inclusion criteria: written in English, describe PIDST patients, specify the method of dural closure, report rates of CSF leak, and be published between 2015 and 2020. Articles were excluded if they had <5 patients. We used standardized toolkits to assess the risk of bias. We assessed patient baseline characteristics, tumor pathology, CSF leak rate, and dural closure techniques; analysis of variance and a 1-way Fisher exact test were used. RESULTS: A total of 4 studies (201 patients) satisfied the inclusion criteria. One study utilized artificial dura (AD) and fibrin glue to perform WTC and CSF diversion, with lumbar drainage as needed. The rate of CSF leak was different among the 4 studies (P=0.017). The study using AD with dural closure adjunct (DCA) for WTC was associated with higher CSF leak rates than those using native dura (ND) with DCA. There was no difference in CSF leak rate between ND-WTC and AD-DCA, or with any of the ND-DCA studies. CONCLUSIONS: After resection of PIDSTs, the use of autologous fat grafts with ND resulted in lower rates of CSF leak, while use of fibrin glue and AD resulted in the highest rates. These characteristics suggest that a component of hydrophobic scaffolding may be required for WTC. A limitation included articles with low levels of evidence. Continued investigation to understand mechanisms for WTC is warranted. LEVEL OF EVIDENCE: Level 3.

Glioblastoma may evade immune surveillance through primary cilia-dependent signaling in an IL-6 dependent manner.

Glioblastoma is the most common, malignant primary brain tumor in adults and remains universally fatal. While immunotherapy has vastly improved the treatment of several solid cancers, efficacy in glioblastoma is limited. These challenges are due in part to the propensity of glioblastoma to recruit tumor-suppressive immune cells, which act in conjunction with tumor cells to create a pro-tumor immune microenvironment through secretion of several soluble factors. Glioblastoma-derived EVs induce myeloid-derived suppressor cells (MDSCs) and non-classical monocytes (NCMs) from myeloid precursors leading to systemic and local immunosuppression. This process is mediated by IL-6 which contributes to the recruitment of tumor-associated macrophages of the M2 immunosuppressive subtype, which in turn, upregulates anti-inflammatory cytokines including IL-10 and TGF-ß. Primary cilia are highly conserved organelles involved in signal transduction and play critical roles in glioblastoma proliferation, invasion, angiogenesis, and chemoradiation resistance. In this perspectives article, we provide preliminary evidence that primary cilia regulate intracellular release of IL-6. This ties primary cilia mechanistically to tumor-mediated immunosuppression in glioblastomas and potentially, in additional neoplasms which have a shared mechanism for cancer-mediated immunosuppression. We propose potentially testable hypotheses of the cellular mechanisms behind this finding.