Background: Relapsed medulloblastoma (MB) poses a significant therapeutic challenge due to its highly immunosuppressive tumor microenvironment. Immune checkpoint inhibitors (ICIs) have struggled to mitigate this challenge, largely due to low T-cell infiltration and minimal PD-L1 expression. Identifying the mechanisms driving low T-cell infiltration is crucial for developing more effective immunotherapies. Methods: We utilize a syngeneic mouse model to investigate the tumor immune microenvironment of MB and compare our findings to transcriptomic and proteomic data from human MB. Results: Flow cytometry reveals a notable presence of CD45^hi/CD11b^hi macrophage-like and CD45^int/CD11b^int microglia-like tumor-associated macrophages (TAMs), alongside regulatory T-cells (T_regs), expressing high levels of the inhibitory checkpoint molecule VISTA. Compared to sham control mice, the CD45^hi/CD11b^hi compartment significantly expands in tumor-bearing mice and exhibits a myeloid-specific signature composed of VISTA, CD80, PD-L1, CTLA-4, MHCII, CD40, and CD68. These findings are corroborated by proteomic and transcriptomic analyses of human MB samples. Immunohistochemistry highlights an abundance of VISTA-expressing myeloid cells clustering at the tumor–cerebellar border, while T-cells are scarce and express FOXP3. Additionally, tumor cells exhibit immunosuppressive properties, inhibiting CD4 T-cell proliferation in vitro. Identification of VISTA’s binding partner, VSIG8, on tumor cells, and its correlation with increased VISTA expression in human transcriptomic analyses suggests a potential therapeutic target. Conclusions: This study underscores the multifaceted mechanisms of immune evasion in MB and highlights the therapeutic potential of targeting the VISTA–VSIG axis to enhance anti-tumor responses.

Disparities in neurosurgical care are increasingly recognized, yet how they affect the diagnosis and management of vestibular schwannoma (VS) remains unclear. Differences in tumor size at diagnosis, treatment selection, and outcomes may be influenced by race, insurance status, income, and geography. To date, no comprehensive synthesis has addressed these inequities in patients with sporadic VS. To systematically evaluate the literature for evidence of social determinants of health (SDoH) in the diagnosis, treatment, and outcomes of patients with sporadic vestibular schwannoma. We conducted a PRISMA-guided systematic review of PubMed, Embase, and Web of Science (2000–2024). Included studies examined adult patients with sporadic VS and reported at least one socioeconomic variable. Non-English studies and those involving pediatric patients were excluded. Studies focusing on neurofibromatosis type 2 were excluded. Screening and data extraction were conducted independently by multiple reviewers using Covidence. Outcomes of interest included tumor size, treatment modality (surgery, radiosurgery, observation), hearing preservation, complications, and recurrence. Study quality was assessed using the GRADE framework and evaluated across the domains of risk of bias, inconsistency, indirectness, imprecision, and publication bias. Of 487 records identified, 40 met inclusion criteria. Most were US-based, retrospective studies that utilized national databases for patient recruitment. Race and insurance status were the most frequently reported variables; income and geographic indicators were less commonly assessed. Outcomes described the likelihood of treatment received, including surgery or SRS, complications including morbidity and mortality, length of stay, and discharge disposition including rehab and readmission. Few studies assessed functional status ( n =2), hearing outcomes ( n =2), or quality of life (n=1). In total, 358,843 patients were included across the 40 studies analyzed. This review suggests that disparities in vestibular schwannoma care are multi-factorial, with race and insurance status showing the most consistent associations between management, outcomes, and disparities. As treatment continues to evolve and become more centralized, future work should prioritize multi-institutional studies to incorporate patient-level socioeconomic data and evaluate outcomes beyond management selection.