RNA aggregates harness the danger response for potent cancer immunotherapy.

Cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Here, we create "onion-like" multi-lamellar RNA lipid particle aggregates (LPAs) to substantially enhance the payload packaging and immunogenicity of tumor mRNA antigens. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for Toll-like receptor engagement in immune cells, systemically administered RNA-LPAs activate RIG-I in stromal cells, eliciting massive cytokine/chemokine response and dendritic cell/lymphocyte trafficking that provokes cancer immunogenicity and mediates rejection of both early- and late-stage murine tumor models. In client-owned canines with terminal gliomas, RNA-LPAs improved survivorship and reprogrammed the TME, which became "hot" within days of a single infusion. In a first-in-human trial, RNA-LPAs elicited rapid cytokine/chemokine release, immune activation/trafficking, tissue-confirmed pseudoprogression, and glioma-specific immune responses in glioblastoma patients. These data support RNA-LPAs as a new technology that simultaneously reprograms the TME while eliciting rapid and enduring cancer immunotherapy.

An Interdisciplinary Protocol for Ventriculoperitoneal Shunt Patient Selection in Normal Pressure Hydrocephalus.

BACKGROUND: Normal pressure hydrocephalus can be treated with ventriculoperitoneal shunt (VPS) placement, but no broadly implemented indication for VPS exists. METHODS: Our protocol consists of physical therapy and occupational therapy practitioners administering validated tests of gait, balance, and cognition before and after lumbar drain placement. Specific tests include: Timed "Up & Go", Tinetti Gait and Balance Assessment, Berg Balance Scale, Mini Mental Status Exam, Trail Making Test Part B, and the Rey Auditory and Visual Learning Test. Minimal clinically important difference values for each test were determined from literature review. A retrospective review of patients treated under this protocol was performed. The primary outcomes were candidacy for VPS based on the protocol and patient-reported symptomatic improvement after VPS placement. RESULTS: A total of 48/75 (64%) patients received VPS. A total of 43/48 (89.6%) of those shunted reported improved symptoms at 6-week follow-up. However, 10/22 (45.5%) reported worsening symptoms at 1-year follow-up. The mean Tinetti score significantly increased after lumbar drain in patients who improved with VPS compared to the no shunt group (4.27 vs. -0.48, P < 0.001). A total of 6/33 (18%) patients with postoperative imaging had a subdural fluid collection identified and 3/49 (6%) had other complications, including 1 seizure, 1 intracerebral hemorrhage, and 1 stroke. CONCLUSIONS: Standardized assessment of gait, balance, and cognition before and after temporary cerebrospinal fluid diversion identifies patients with normal pressure hydrocephalus likely to benefit from VPS placement with a low complication rate. One year after VPS, approximately one half of patients had symptoms recurrence.

Academic accomplishments of Black neurosurgeons in the United States.

OBJECTIVE: Neurosurgery has remained relatively homogeneous in terms of racial and gender diversity, trailing behind national demographics. Less than 5% of practicing neurosurgeons in the United States identify as Black/African American (AA). Research and academic productivity are highly emphasized within the field and are crucial for career advancement at academic institutions. They also serve as important avenues for mentorship and recruitment of diverse trainees and medical students. This study aimed to summarize the academic accomplishments of AA neurosurgeons by assessing publication quantity, h-index, and federal grant funding. METHODS: One hundred thirteen neurosurgery residency training programs accredited by the Accreditation Council for Graduate Medical Education in 2022 were included in this study. The American Society of Black Neurosurgeons registry was reviewed to analyze the academic metrics of self-identified Black or AA academic neurosurgeons. Data on the academic rank, leadership position, publication quantity, h-index, and race of neurosurgical faculty in the US were obtained from publicly available information and program websites. RESULTS: Fifty-five AA and 1393 non-AA neurosurgeons were identified. Sixty percent of AA neurosurgeons were fewer than 10 years out from residency training, compared to 37.4% of non-AA neurosurgeons (p = 0.001). AA neurosurgeons had a median 32 (IQR 9, 85) publications compared to 52 (IQR 22, 122) for non-AA neurosurgeons (p = 0.019). AA neurosurgeons had a median h-index of 12 (IQR 5, 24) compared to 16 (IQR 9, 31) for non-AA colleagues (p = 0.02). Following stratification by academic rank, these trends did not persist. No statistically significant differences in the median amounts of awarded National Institutes of Health funding (p = 0.194) or level of professorship attained (p = 0.07) were observed between the two cohorts. CONCLUSIONS: Racial disparities between AA and non-AA neurosurgeons exist in publication quantity and h-index overall but not when these groups are stratified by academic rank. Given that AA neurosurgeons comprise more junior faculty, it is expected that their academic accomplishments will increase as more enter academic practice and current neurosurgeons advance into more senior positions.

Vaccines: a promising therapy for myelodysplastic syndrome.

Myelodysplastic neoplasms (MDS) define clonal hematopoietic malignancies characterized by heterogeneous mutational and clinical spectra typically seen in the elderly. Curative treatment entails allogeneic hematopoietic stem cell transplant, which is often not a feasible option due to older age and significant comorbidities. Immunotherapy has the cytotoxic capacity to elicit tumor-specific killing with long-term immunological memory. While a number of platforms have emerged, therapeutic vaccination presents as an appealing strategy for MDS given its promising safety profile and amenability for commercialization. Several preclinical and clinical trials have investigated the efficacy of vaccines in MDS; these include peptide vaccines targeting tumor antigens, whole cell-based vaccines and dendritic cell-based vaccines. These therapeutic vaccines have shown acceptable safety profiles, but consistent clinical responses remain elusive despite robust immunological reactions. Combining vaccines with immunotherapeutic agents holds promise and requires further investigation. Herein, we highlight therapeutic vaccine trials while reviewing challenges and future directions of successful vaccination strategies in MDS.

The Safety and Efficacy of Concurrent Immune Checkpoint Blockade and Stereotactic Radiosurgery Therapy with Practitioner and Researcher Recommendations.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have shown growing promise in the treatment of brain metastases, especially combined with stereotactic radiosurgery (SRS). The combination of ICIs with SRS has been studied for efficacy as well as increasing radiation necrosis risks. In this review, we compare clinical outcomes of radiation necrosis, intracranial control, and overall survival between patients with brain metastases treated with either SRS alone or SRS-ICI combination therapy. METHODS: A literature search of PubMed, Scopus, Embase, Web of Science, and Cochrane was performed in May 2023 for articles comparing the safety and efficacy of SRS/ICI versus SRS-alone for treating brain metastases. RESULTS: The search criteria identified 1961 articles, of which 48 met inclusion criteria. Combination therapy with SRS and ICI does not lead to significant increases in incidence of radiation necrosis either radiographically or symptomatically. Overall, no difference was found in intracranial control between SRS-alone and SRS-ICI combination therapy. Combination therapy is associated with increased median overall survival. Notably, some comparative studies observed decreased neurologic deaths, challenging presumptions that improved survival is due to greater systemic control. The literature supports SRS-ICI administration within 4 weeks of another for survival but remains inconclusive, requiring further study for other outcome measures. CONCLUSIONS: Combination SRS-ICI therapy is associated with significant overall survival benefit for patients with brain metastases without significantly increasing radiation necrosis risks compared to SRS alone. Although intracranial control rates appear to be similar between the 2 groups, timing of treatment delivery may improve control rates and demands further study attention.

Patterns and predictors of anxiety and depression symptom trajectories in patients diagnosed with primary brain tumors.

BACKGROUND: Patients with primary brain tumors (pPBTs) often exhibit heightened distress. This study assesses how symptoms of anxiety and depression change over time in pPBTs and identifies factors that may predict patients' symptom trajectories. METHODS: Ninety-nine adult pPBTs completed psychosocial assessments at neuro-oncology appointments over 6-18 months. Quality of life was assessed with the Functional Assessment of Cancer Therapy-Brain; symptoms of anxiety and depression were assessed with the Patient-Reported Outcomes Measurement Information System short forms. The prevalence of patients with clinically elevated symptoms and those who experienced clinically meaningful changes in symptoms throughout follow-up were examined. Linear mixed-effects models evaluated changes in symptoms over time at the group level, and latent class growth analysis (LCGA) evaluated changes in symptoms over time at the individual level. RESULTS: At enrollment, 51.5% and 32.3% of patients exhibited clinically elevated levels of anxiety and depression, respectively. Of patients with follow-up data (n = 74), 54.1% and 50% experienced clinically meaningful increases in anxiety and depression scores, respectively. There were no significant changes in anxiety or depression scores over time, but better physical, functional, and brain-cancer well-being predicted lower levels of anxiety and depression (p < 0.001). Five sub-groups of patients with distinct symptom trajectories emerged via LCGA. CONCLUSIONS: pPBTs commonly experience elevated symptoms of anxiety and depression that may fluctuate in clinically meaningful manners throughout the disease. Routine screening for elevated symptoms is needed to capture clinically meaningful changes and identify factors affecting symptoms to intervene on.

Clinical management of seizures in patients with meningiomas: Efficacy of surgical resection for seizure control and patient-tailored postoperative anti-epileptic drug management.

Meningiomas are the most common primary intracranial tumor. They are slow growing and often incidentally found tumors that arise from the arachnoid villi. As they grow, they have a greater likelihood of becoming symptomatic with seizures being one of the most clinically significant symptoms. Seizures are more likely to present as a symptom of larger meningiomas and meningiomas that compress cortical areas particularly those in non-skull base locations. These seizures are often managed medically, utilizing the same anti-seizure medications that are used to treat other causes of epilepsy. We discuss common anti-seizure medications used including valproate, phenobarbital, carbamazepine, phenytoin, lacosamide, lamotrigine, levetiracetam and topiramate and their common adverse effects. The goal of pharmacotherapy for seizure control is to maximize seizure control while minimizing the adverse effects of the medication. The decision to provide medical management is dependent on individual seizure history and plans for surgical treatment. Patients who did not require seizure prophylaxis before surgery are commonly prescribed seizure prophylaxis postoperatively. Symptomatic meningiomas not controlled by medical management alone are commonly evaluated for surgical resection. The efficacy of surgical resection in providing seizure freedom is dependent on several features of the tumor including tumor size, the extent of the peritumoral edema, the number of tumors, sinus infiltration and the degree of resection.

mRNA challenge predicts brain cancer immunogenicity and response to checkpoint inhibitors.

To prospectively determine whether brain tumors will respond to immune checkpoint inhibitors (ICIs), we developed a novel mRNA vaccine as a viral mimic to elucidate cytokine release from brain cancer cells in vitro. Our results indicate that cytokine signatures following mRNA challenge differ substantially from ICI responsive versus non-responsive murine tumors. These findings allow for creation of a diagnostic assay to quickly assess brain tumor immunogenicity, allowing for informed treatment with ICI or lack thereof in poorly immunogenic settings.

mRNA aggregates harness danger response for potent cancer immunotherapy.

Messenger RNA (mRNA) has emerged as a remarkable tool for COVID-19 prevention but its use for induction of therapeutic cancer immunotherapy remains limited by poor antigenicity and a regulatory tumor microenvironment (TME). Herein, we develop a facile approach for substantially enhancing immunogenicity of tumor-derived mRNA in lipid-particle (LP) delivery systems. By using mRNA as a molecular bridge with ultrapure liposomes and foregoing helper lipids, we promote the formation of 'onion-like' multi-lamellar RNA-LP aggregates (LPA). Intravenous administration of RNA-LPAs mimics infectious emboli and elicits massive DC/T cell mobilization into lymphoid tissues provoking cancer immunogenicity and mediating rejection of both early and late-stage murine tumor models. Unlike current mRNA vaccine designs that rely on payload packaging into nanoparticle cores for toll-like receptor engagement, RNA-LPAs stimulate intracellular pathogen recognition receptors (RIG-I) and reprogram the TME thus enabling therapeutic T cell activity. RNA-LPAs were safe in acute/chronic murine GLP toxicology studies and immunologically active in client-owned canines with terminal gliomas. In an early phase first-in-human trial for patients with glioblastoma, we show that RNA-LPAs encoding for tumor-associated antigens elicit rapid induction of pro-inflammatory cytokines, mobilization/activation of monocytes and lymphocytes, and expansion of antigen-specific T cell immunity. These data support the use of RNA-LPAs as novel tools to elicit and sustain immune responses against poorly immunogenic tumors.

Transseptal puncture during catheter ablation associated with higher radiation exposure.

BACKGROUND: Electroanatomic mapping systems are increasingly used during ablations to decrease the need for fluoroscopy and therefore radiation exposure. For left-sided arrhythmias, transseptal puncture is a common procedure performed to gain access to the left side of the heart. We aimed to demonstrate the radiation exposure associated with transseptal puncture. METHODS: Data were retrospectively collected from the Catheter Ablation with Reduction or Elimination of Fluoroscopy registry. Patients with left-sided accessory pathway-mediated tachycardia, with a structurally normal heart, who had a transseptal puncture, and were under 22 years of age were included. Those with previous ablations, concurrent diagnostic or interventional catheterisation, and missing data for fluoroscopy use or procedural outcomes were excluded. Patients with a patent foramen ovale who did not have a transseptal puncture were selected as the control group using the same criteria. Procedural outcomes were compared between the two groups. RESULTS: There were 284 patients in the transseptal puncture group and 70 in the patent foramen ovale group. The transseptal puncture group had a significantly higher mean procedure time (158.8 versus 131.4 minutes, p = 0.002), rate of fluoroscopy use (38% versus 7%, p < 0.001), and mean fluoroscopy time (2.4 versus 0.6 minutes, p < 0.001). The acute success and complication rates were similar. CONCLUSIONS: Performing transseptal puncture remains a common reason to utilise fluoroscopy in the era of non-fluoroscopic ablation. Better tools are needed to make non-fluoroscopic transseptal puncture more feasible.

Duration of Prophylactic Levetiracetam After Surgery for Brain Tumor: A Prospective Randomized Trial.

BACKGROUND: Levetiracetam is commonly used as a prophylactic antiseizure medication in patients undergoing surgical resection of brain tumors. OBJECTIVE: To quantitate side effects experienced in patients treated with 1 week vs 6 weeks of prophylactic levetiracetam using validated measures for neurotoxicity and depression. METHODS: Patients undergoing surgical resection of a supratentorial tumor with no seizure history were randomized within 48 hours of surgery to receive prophylactic levetiracetam for the duration of either 1 or 6 weeks. Patients were given oral levetiracetam extended release 1000 mg during the first part of this study. Owing to drug backorder, patients enrolled later in this study received levetiracetam 500 mg BID. The primary outcome was the change in the neurotoxicity score 6 weeks after drug initiation. The secondary outcome was seizure incidence. RESULTS: A total of 81 patients were enrolled and randomized to 1 week (40 patients) or 6 weeks (41 patients) of prophylactic levetiracetam treatment. The neurotoxicity score slightly improved in the overall cohort between baseline and reassessment. There was no significant difference between groups in neurotoxicity or depression scores. Seizure incidence was low in the entire cohort of patients with 1 patient in each arm experiencing a seizure during the follow-up period. CONCLUSION: The use of prophylactic levetiracetam did not result in significant neurotoxicity or depression when given for either 1 week or 6 weeks. The incidence of seizure after craniotomy for tumor resection is low regardless of duration of therapy.

Heterogeneity of glioblastoma stem cells in the context of the immune microenvironment and geospatial organization.

Glioblastoma (GBM) is an extremely aggressive and incurable primary brain tumor with a 10-year survival of just 0.71%. Cancer stem cells (CSCs) are thought to seed GBM's inevitable recurrence by evading standard of care treatment, which combines surgical resection, radiotherapy, and chemotherapy, contributing to this grim prognosis. Effective targeting of CSCs could result in insights into GBM treatment resistance and development of novel treatment paradigms. There is a major ongoing effort to characterize CSCs, understand their interactions with the tumor microenvironment, and identify ways to eliminate them. This review discusses the diversity of CSC lineages present in GBM and how this glioma stem cell (GSC) mosaicism drives global intratumoral heterogeneity constituted by complex and spatially distinct local microenvironments. We review how a tumor's diverse CSC populations orchestrate and interact with the environment, especially the immune landscape. We also discuss how to map this intricate GBM ecosystem through the lens of metabolism and immunology to find vulnerabilities and new ways to disrupt the equilibrium of the system to achieve improved disease outcome.

Histologic Findings at the Time of Repeat Resection Predicts Survival in Patients with Glioblastoma.

OBJECTIVE: Radiographic worsening in patients with glioblastoma undergoing treatment may be due to tumor recurrence or treatment effect. The overall prognosis of these patients based on histologic findings at the time of repeat resection is not well established. METHODS: Patients with glioblastoma at our institution were identified. Patients who only had 1 surgery were excluded. Demographic and clinical data were recorded. The histologic diagnosis at the time of repeat surgery was recorded as either tumor recurrence or pseudoprogression. For this study, pseudoprogression was defined as absence of tumor histologic features and could show coagulative necrosis, reactive gliosis, and/or inflammatory infiltration. RESULTS: A total of 115 patients were identified, 106 with tumor recurrence and 9 with pseudoprogression. The pseudoprogression group had a greater percentage of patients with O6-methylguanine DNA-methyltransferase (MGMT) methylation (37.7% vs. 66.7%), but these results did not reach statistical significance. The overall median survival was 23.1 months. The overall median survival was 22.0 months in the tumor recurrence group and 33.3 months in the pseudoprogression group (P = 0.0814). The overall median survival from the time of repeat surgery was 8.4 months for the entire cohort, 8.3 months for the tumor recurrence group and 18.4 months for the pseudoprogression group (P = 0.0063). In multivariable analysis, presence of tumor features was predictive of worse overall survival from the time of second surgery (hazards ratio 3.96, 95% confidence interval: 1.30-12.06, P = 0.0156). CONCLUSIONS: In patients with worsening imaging, the absence of tumor on histologic diagnosis is associated with improved survival from the time of second surgery.

Clival Paraganglioma, Case Report and Literature Review.

Paragangliomas are rare tumors that may present with cranial neuropathies when located along the skull base. Supratentorial paragangliomas are less likely to secrete catecholamines but should be worked up, nonetheless. We highlight a case of a female in her fourth decade found to have a petroclival lesion following initial presentation that included one month of tooth pain, dysphagia, diplopia, hoarseness and right hemifacial hypoesthesia. Magnetic resonance imaging of the brain demonstrated a T2 hyperintense lesion favored to be a petroclival meningioma. Pre-operative angiography demonstrated a hypervascular tumor. She underwent a combined presigmoid craniotomy with posterior petrosectomy performed by both neurosurgery and neuro-otology. Pathology demonstrated paraganglioma. She had small volume residual tumor and is planned for continued outpatient radiotherapy. Paragangliomas should be on the differential for skull base lesions. Management paradigm involves multidisciplinary care and a combination of surgical resection and post-operative radiation. In this paper, we discuss underlying pathophysiology as well as appropriate workup and management.

The trial effect in patients with glioblastoma: effect of clinical trial enrollment on overall survival.

PURPOSE: To determine whether participation in a clinical trial was associated with improved survival in patients with glioblastoma (GBM). METHODS: Following IRB approval, patients were identified using CPT and ICD codes. Data was collected using retrospective review of electronic medical records. When necessary, death data was obtained from online obituaries. Inverse propensity score matching was utilized to transform the two cohorts to comparable sets. Survival was compared using Kaplan-Meyer curves and Wilcoxon Rank Sum Test. RESULTS: In this cohort of 365 patients, 89 were enrolled in a clinical trial and 276 were not. Patients enrolled in clinical trials had a significantly higher mean baseline KPS score, higher proportion of surgical resections, and were more likely to receive temozolomide treatment than patients not enrolled in a clinical trial. After inverse propensity score matching, patients enrolled in a clinical trial lived significantly longer than those not enrolled (28.8 vs 22.2 months, p = 0.005). A potential confounder of this study is that patients not in a clinical trial had significantly fewer visits with neuro-oncologists than patients enrolled in a clinical trial (7 ± 8 vs 12 ± 9, p < 0. 0001). CONCLUSIONS: Clinical trials enroll patients with the most favorable prognostic features. Even when correcting for this bias, clinical trial enrollment is an independent predictor of increased survival regardless of treatment arm.

Visualization of the perivenous glymphatic efflux in human brain after laser interstitial thermal therapy.

Recent studies have revealed that there is existence of a specific waste clearance pathway in the brain, coined the glymphatic system. This case report demonstrates supportive finding of drainage of Gadolinium and waste products released after Laser Interstitial Thermal Therapy via perivenous routes and a paradural lymphatic system. These findings provide further evidence of interstitial fluid drainage along the perivenous spaces in accordance with a glymphatic system theory.

Slow-Cycling Cells in Glioblastoma: A Specific Population in the Cellular Mosaic of Cancer Stem Cells.

Glioblastoma (GBM) exhibits populations of cells that drive tumorigenesis, treatment resistance, and disease progression. Cells with such properties have been described to express specific surface and intracellular markers or exhibit specific functional states, including being slow-cycling or quiescent with the ability to generate proliferative progenies. In GBM, each of these cellular fractions was shown to harbor cardinal features of cancer stem cells (CSCs). In this study, we focus on the comparison of these cells and present evidence of great phenotypic and functional heterogeneity in brain cancer cell populations with stemness properties, especially between slow-cycling cells (SCCs) and cells phenotypically defined based on the expression of markers commonly used to enrich for CSCs. Here, we present an integrative analysis of the heterogeneity present in GBM cancer stem cell populations using a combination of approaches including flow cytometry, bulk RNA sequencing, and single cell transcriptomics completed with functional assays. We demonstrated that SCCs exhibit a diverse range of expression levels of canonical CSC markers. Importantly, the property of being slow-cycling and the expression of these markers were not mutually inclusive. We interrogated a single-cell RNA sequencing dataset and defined a group of cells as SCCs based on the highest score of a specific metabolic signature. Multiple CSC groups were determined based on the highest expression level of CD133, SOX2, PTPRZ1, ITGB8, or CD44. Each group, composed of 22 cells, showed limited cellular overlap, with SCCs representing a unique population with none of the 22 cells being included in the other groups. We also found transcriptomic distinctions between populations, which correlated with clinicopathological features of GBM. Patients with strong SCC signature score were associated with shorter survival and clustered within the mesenchymal molecular subtype. Cellular diversity amongst these populations was also demonstrated functionally, as illustrated by the heterogenous response to the chemotherapeutic agent temozolomide. In conclusion, our study supports the cancer stem cell mosaicism model, with slow-cycling cells representing critical elements harboring key features of disseminating cells.

Tumor Treating Fields dually activate STING and AIM2 inflammasomes to induce adjuvant immunity in glioblastoma.

Tumor Treating Fields (TTFields), an approved therapy for glioblastoma (GBM) and malignant mesothelioma, employ noninvasive application of low-intensity, intermediate-frequency, alternating electric fields to disrupt the mitotic spindle, leading to chromosome missegregation and apoptosis. Emerging evidence suggests that TTFields may also induce inflammation. However, the mechanism underlying this property and whether it can be harnessed therapeutically are unclear. Here, we report that TTFields induced focal disruption of the nuclear envelope, leading to cytosolic release of large micronuclei clusters that intensely recruited and activated 2 major DNA sensors - cyclic GMP-AMP synthase (cGAS) and absent in melanoma 2 (AIM2) - and their cognate cGAS/stimulator of interferon genes (STING) and AIM2/caspase 1 inflammasomes to produce proinflammatory cytokines, type 1 interferons (T1IFNs), and T1IFN-responsive genes. In syngeneic murine GBM models, TTFields-treated GBM cells induced antitumor memory immunity and a cure rate of 42% to 66% in a STING- and AIM2-dependent manner. Using single-cell and bulk RNA sequencing of peripheral blood mononuclear cells, we detected robust post-TTFields activation of adaptive immunity in patients with GBM via a T1IFN-based trajectory and identified a gene panel signature of TTFields effects on T cell activation and clonal expansion. Collectively, these studies defined a therapeutic strategy using TTFields as cancer immunotherapy in GBM and potentially other solid tumors.

Glioma Immunotherapy: Advances and Challenges for Spinal Cord Gliomas.

Spinal cord gliomas are rare entities that often have limited surgical options. Immunotherapy has shown promise in intracranial gliomas with some research suggesting benefit for spinal cord gliomas. A focused review of immunotherapies that have been investigated in spinal cord gliomas was performed. The primary methods of immunotherapy investigated in spinal cord gliomas include immune checkpoint inhibitors, adoptive T-cell therapies, and vaccine strategies. There are innumerable challenges that must be overcome to effectively apply immunotherapeutic strategies to the spinal cord gliomas including low incidence, few antigenic targets, the blood spinal cord barrier, the immunosuppressive tumor microenvironment and neurotoxic treatment effects. Nonetheless, research has suggested ways to overcome these challenges and treatments have been effective in case reports for metastatic non-small cell lung cancer, melanoma, midline glioma and glioblastoma. Current therapies for spinal cord gliomas are markedly limited. Further research is needed to determine if the success of immunotherapy for intracranial gliomas can be effectively applied to these unique tumors.