A T-cell antigen atlas for meningioma: novel options for immunotherapy.

Meningiomas are the most common primary intracranial tumors. Although most symptomatic cases can be managed by surgery and/or radiotherapy, a relevant number of patients experience an unfavorable clinical course and additional treatment options are needed. As meningiomas are often perfused by dural branches of the external carotid artery, which is located outside the blood-brain barrier, they might be an accessible target for immunotherapy. However, the landscape of naturally presented tumor antigens in meningioma is unknown. We here provide a T-cell antigen atlas for meningioma by in-depth profiling of the naturally presented immunopeptidome using LC-MS/MS. Candidate target antigens were selected based on a comparative approach using an extensive immunopeptidome data set of normal tissues. Meningioma-exclusive antigens for HLA class I and II are described here for the first time. Top-ranking targets were further functionally characterized by showing their immunogenicity through in vitro T-cell priming assays. Thus, we provide an atlas of meningioma T-cell antigens which will be publicly available for further research. In addition, we have identified novel actionable targets that warrant further investigation as an immunotherapy option for meningioma.

Association of extent of resection on recurrence-free survival and functional outcome in vestibular schwannoma of the elderly.

Background: Despite the ongoing debate on the risk-benefit ratio of vestibular schwannoma (VS) treatment options, watchful observation and radiation are usually favored in the elderly (>65 years). If surgery is inevitable, a multimodal approach after deliberate subtotal resection has been described as a valid option. The relationship between the extent of resection (EOR) of surgical and functional outcomes and recurrence-free survival (RFS) remains unclear. This present study aims to evaluate the functional outcome and RFS of the elderly in relation to the EOR. Methods: This matched cohort study analyzed all consecutive elderly VS patients treated at a tertiary referral center since 2005. A separate cohort (<65 years) served as a matched control group (young). Clinical status was assessed by the Charlson Comorbidity Index (CCI), the Karnofsky Performance (KPS), and the Gardner and Robertson (GR) and House & Brackmann (H&B) scales. RFS was evaluated by Kaplan-Meier analysis using contrast-enhanced magnetic resonance imaging to identify tumor recurrence. Results: Among 2,191 patients, 296 (14%) patients were classified as elderly, of whom 133 (41%) were treated surgically. The elderly were characterized by a higher preoperative morbidity and worse gait uncertainty. Postoperative mortality (0.8% and 1%), morbidity (13% and 14%), and the functional outcome (G&R, H&B, and KPS) did not differ between the elderly and the young. There was a significant benefit in regard to the preoperative imbalance. Gross total resection (GTR) was accomplished in 74% of all cases. Lower grades of the EOR (subtotal and decompressive surgery) raised the incidence of recurrence significantly. Mean time to recurrence in the surgELDERLY was 67.33 ± 42.02 months and 63.2 ± 70.98 months in the surgCONTROL. Conclusions: Surgical VS treatment aiming for complete tumor resection is feasible and safe, even in advanced age. A higher EOR is not associated with cranial nerve deterioration in the elderly compared to the young. In contrast, the EOR determines RFS and the incidence of recurrence/progression in both study cohorts. If surgery is indicated in the elderly, GTR can be intended safely, and if only subtotal resection is achieved, further adjuvant therapy, e.g., radiotherapy, should be discussed in the elderly, as the incidence of recurrence is not significantly lower compared to the young.

Sex-related differences in postoperative complications following elective craniotomy for intracranial lesions: An observational study.

INTRODUCTION: The integration of sex-related differences in neurosurgery is crucial for new, possible sex-specific, therapeutic approaches. In neurosurgical emergencies, such as traumatic brain injury and aneurysmal subarachnoid hemorrhage, these differences have been investigated. So far, little is known concerning the impact of sex on frequency of postoperative complications after elective craniotomy. This study investigates whether sex-related differences exist in frequency of postoperative complications in patients who underwent elective craniotomy for intracranial lesion. MATERIAL AND METHODS: All consecutive patients who underwent an elective intracranial procedure over a 2-year period at our center were eligible for inclusion in this retrospective study. Demographic data, comorbidities, frequency of postoperative complications at 24 hours following surgery and at discharge, and hospital length of stay were compared among females and males. RESULTS: Overall, 664 patients were considered for the analysis. Of those, 339 (50.2%) were females. Demographic data were comparable among females and males. More females than males suffered from allergic, muscular, and rheumatic disorders. No differences in frequency of postoperative complications at 24 hours after surgery and at discharge were observed among females and males. Similarly, the hospital length of stay was comparable. CONCLUSIONS: In the present study, no sex-related differences in frequency of early postoperative complications and at discharge following elective craniotomy for intracranial lesions were observed.

Sex-Related Differences in Patients' Characteristics, Provided Care, and Outcomes Following Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Sex-related differences in patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH) are poorly investigated so far. This study elucidates whether sex-related differences in ICH care in a neurocritical care setting exist, particularly regarding provided care, while also taking patient characteristics, and outcomes into account. METHODS: This retrospective single center study includes all consecutive patients with spontaneous ICH admitted to the neurocritical care unit in a 10-year period. Patients' demographics, comorbidities, symptoms at presentation, radiological findings, surgical and medical provided care, intensive care unit mortality and 12 month-mortality, and functional outcome at discharge were compared among men and women. RESULTS: Overall, 398 patients were included (male = 198 and female = 200). No differences in demographics, Charlson Comorbidity Index (CCI), symptoms at presentation, radiological findings, intensive care unit mortality and 12-month mortality were observed among men and women. Men received an external ventricular drain (EVD) for hydrocephalus-therapy significantly more often than women, despite similar location of the ICH and radiographic parameters. In the multivariate analysis, EVD insertion was independently associated with male sex (odds ratio 2.82, 95% confidence interval 1.61-4.95, P < 0.001) irrespective of demographic or radiological features. Functional outcome after ICH as assessed by the modified Rankin scale, was more favorable for women (P = 0.044). CONCLUSIONS: Sex-related differences in patients with ICH regarding to provided neurosurgical care exist. We provide evidence that insertion of EVD is associated with male sex, disregarding clear reasoning. A sex-bias as well as social factors may play a significant role in decision-making for the insertion of an EVD.

The natural HLA ligandome of glioblastoma stem-like cells: antigen discovery for T cell-based immunotherapy.

Glioblastoma is the most frequent malignant primary brain tumor. In a hierarchical tumor model, glioblastoma stem-like cells (GSC) play a major role in tumor initiation and maintenance as well as in therapy resistance and recurrence. Thus, targeting this cellular subset may be key to effective immunotherapy. Here, we present a mass spectrometry-based analysis of HLA-presented peptidomes of GSC and glioblastoma patient specimens. Based on the analysis of patient samples (n = 9) and GSC (n = 3), we performed comparative HLA peptidome profiling against a dataset of normal human tissues. Using this immunopeptidome-centric approach we could clearly delineate a subset of naturally presented, GSC-associated HLA ligands, which might serve as highly specific targets for T cell-based immunotherapy. In total, we identified 17 antigens represented by 41 different HLA ligands showing natural and exclusive presentation both on GSC and patient samples. Importantly, in vitro immunogenicity and antigen-specific target cell killing assays suggest these peptides to be epitopes of functional CD8+ T cell responses, thus rendering them prime candidates for antigen-specific immunotherapy of glioblastoma.