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CNS Neuroscience & Therapeutics Jun 2024Programmed death-ligand 1 (PD-L1) expression is an immune evasion mechanism that has been demonstrated in many tumors and is commonly associated with a poor prognosis....
INTRODUCTION
Programmed death-ligand 1 (PD-L1) expression is an immune evasion mechanism that has been demonstrated in many tumors and is commonly associated with a poor prognosis. Over the years, anti-PD-L1 agents have gained attention as novel anticancer therapeutics that induce durable tumor regression in numerous malignancies. They may be a new treatment choice for neurofibromatosis type 2 (NF2) patients.
AIMS
The aims of this study were to detect the expression of PD-L1 in NF2-associated meningiomas, explore the effect of PD-L1 downregulation on tumor cell characteristics and T-cell functions, and investigate the possible pathways that regulate PD-L1 expression to further dissect the possible mechanism of immune suppression in NF2 tumors and to provide new treatment options for NF2 patients.
RESULTS
PD-L1 is heterogeneously expressed in NF2-associated meningiomas. After PD-L1 knockdown in NF2-associated meningioma cells, tumor cell proliferation was significantly inhibited, and the apoptosis rate was elevated. When T cells were cocultured with siPD-L1-transfected NF2-associated meningioma cells, the expression of CD69 on both CD4 and CD8 T cells was partly reversed, and the capacity of CD8 T cells to kill siPD-L1-transfected tumor cells was partly restored. Results also showed that the PI3K-AKT-mTOR pathway regulates PD-L1 expression, and the mTOR inhibitor rapamycin rapidly and persistently suppresses PD-L1 expression. In vivo experimental results suggested that anti-PD-L1 antibody may have a synergetic effect with the mTOR inhibitor in reducing tumor cell proliferation and that reduced PD-L1 expression could contribute to antitumor efficacy.
CONCLUSIONS
Targeting PD-L1 could be helpful for restoring the function of tumor-infiltrating lymphocytes and inducing apoptosis to inhibit tumor proliferation in NF2-associated meningiomas. Dissecting the mechanisms of the PD-L1-driven tumorigenesis of NF2-associated meningioma will help to improve our understanding of the mechanisms underlying tumor progression and could facilitate further refinement of current therapies to improve the treatment of NF2 patients.
Topics: Meningioma; Humans; B7-H1 Antigen; Cell Proliferation; Meningeal Neoplasms; Animals; T-Lymphocytes; Neurofibromatosis 2; Mice; Male; Female; Neurofibromin 2; Cell Line, Tumor; Middle Aged; Mice, Nude; Apoptosis
PubMed: 38828669
DOI: 10.1111/cns.14784 -
Acta Otorhinolaryngologica Italica :... May 2024
Meta-Analysis
Topics: Humans; Neuroma, Acoustic; Hearing Loss
PubMed: 38745520
DOI: 10.14639/0392-100X-suppl.1-44-2024-N2900 -
Brain Tumor Research and Treatment Apr 2024Vestibular schwannomas (VSs) are the most common cerebellopontine tumors. The natural history of smaller-sized VSs (<30 mm) has been well-studied, leading to the...
Vestibular schwannomas (VSs) are the most common cerebellopontine tumors. The natural history of smaller-sized VSs (<30 mm) has been well-studied, leading to the recommendation of a "watch and wait" approach. However, large VSs (>30 mm) have not been extensively studied, mainly because of their rarity. As such, most patients are conventionally offered surgery which carries a significant risk of neurological morbidity. Here, we report a case of a giant VS (>40 mm) in a 30-year-old man who regressed spontaneously. He was lost to follow-up for 18 years and, upon re-presentation, the symptomatology drastically improved and repeat imaging demonstrated a marked reduction in tumor size. Referring to similar cases in other studies, we postulate that most large and giant VSs undergo a phase of growth and stasis, followed by regression due to shifts in the balance between tumorigenic and regressive factors. Taken together with emerging molecular data, further studies are required to better understand the history of large and giant VSs to shape more personalized treatment options. This potentially includes non-operative management as a tenable option.
PubMed: 38742262
DOI: 10.14791/btrt.2024.0008 -
Scientific Reports May 2024Hearing preservation (HP) during vestibular schwannomas (VSs) surgery poses a significant challenge. Although brainstem auditory evoked potentials (BAEPs) on the...
Hearing preservation (HP) during vestibular schwannomas (VSs) surgery poses a significant challenge. Although brainstem auditory evoked potentials (BAEPs) on the affected side are commonly employed to monitor cochlear nerve function, their low signal-to-noise ratio (SNR) renders them susceptible to interferences, compromising their reliability. We retrospectively analyzed the data of patients who underwent tumor resection, while binaural brainstem auditory evoked potentials (BAEPs) were simultaneously recorded during surgery. To standardize BAEPs on the affected side, we incorporated the synchronous healthy side as a reference (interval between affected and healthy side ≤ 3 min). A total of 127 patients were enrolled. Comparison of the raw BAEPs data pre- and post-tumor resection revealed that neither V-wave amplitude (Am-V) nor latency (La-V) could serve as reliable predictors of HP simultaneously. However, following standardization, V-wave latency (STIAS-La-V) and amplitude (STIAS-Am-V) emerged as stable predictors of HP. Furthermore, the intraoperative difference in V-wave amplitude (D-Am-V) predicted postoperative HP in patients with preoperative HP and remained predictive after standardization. The utilization of intraoperative synchronous healthy side BAEPs as a reference to eliminate interferences proves to be an effective approach in enhancing the reliability of BAEPs for predicting HP in VSs patients.
Topics: Humans; Neuroma, Acoustic; Female; Evoked Potentials, Auditory, Brain Stem; Male; Middle Aged; Adult; Retrospective Studies; Aged; Hearing; Young Adult
PubMed: 38719853
DOI: 10.1038/s41598-024-58531-8 -
Hearing Research Jun 2024Hearing loss is a common side effect of many tumor treatments. However, hearing loss can also occur as a direct result of certain tumors of the nervous system, the most... (Review)
Review
Hearing loss is a common side effect of many tumor treatments. However, hearing loss can also occur as a direct result of certain tumors of the nervous system, the most common of which are the vestibular schwannomas (VS). These tumors arise from Schwann cells of the vestibulocochlear nerve and their main cause is the loss of function of NF2, with 95 % of cases being sporadic and 5 % being part of the rare neurofibromatosis type 2 (NF2)-related Schwannomatosis. Genetic variations in NF2 do not fully explain the clinical heterogeneity of VS, and interactions between Schwann cells and their microenvironment appear to be critical for tumor development. Preclinical in vitro and in vivo models of VS are needed to develop prognostic biomarkers and targeted therapies. In addition to VS, other tumors can affect hearing. Meningiomas and other masses in the cerebellopontine angle can compress the vestibulocochlear nerve due to their anatomic proximity. Gliomas can disrupt several neurological functions, including hearing; in fact, glioblastoma multiforme, the most aggressive subtype, may exhibit early symptoms of auditory alterations. Besides, treatments for high-grade tumors, including chemotherapy or radiotherapy, as well as incomplete resections, can induce long-term auditory dysfunction. Because hearing loss can have an irreversible and dramatic impact on quality of life, it should be considered in the clinical management plan of patients with tumors, and monitored throughout the course of the disease.
Topics: Humans; Neuroma, Acoustic; Hearing Loss; Animals; Hearing; Neurilemmoma; Vestibulocochlear Nerve; Risk Factors; Neurofibromatosis 2; Meningioma
PubMed: 38703433
DOI: 10.1016/j.heares.2024.109012 -
Neurology India Mar 2024
Review
Topics: Humans; Neuroma, Acoustic; Hemorrhage; Magnetic Resonance Imaging; Male; Female
PubMed: 38691495
DOI: 10.4103/NI.Neurol-India-D-23-00294 -
Environment International May 2024Some have looked forward to the publication of the results of the COSMOS study on brain tumors, because the potential biases from retrospective investigations...
Some have looked forward to the publication of the results of the COSMOS study on brain tumors, because the potential biases from retrospective investigations predominating the search for brain tumor risks of mobile phone use since the late 1990 s were deemed unresolvable by further investigations of that type. Indeed, prospective cohort studies typically have the advantage of being not or less affected by differential exposure misclassification, recall and selection bias, and, as they proceed in the direction of the time arrow, results are more easily interpreted in terms of causation. However, results of the COSMOS study published now in this journal are not of help for the risk assessment of mobile phone use and do not support the conclusions of the authors that their findings "suggest that the cumulative amount of mobile phone use is not associated with the risk of developing glioma, meningioma, or acoustic neuroma".
Topics: Brain Neoplasms; Humans; Cell Phone; Prospective Studies; Cohort Studies; Bias; Risk Assessment; Glioma; Meningioma; Neuroma, Acoustic; Radiation Exposure; Young Adult; Adult; Middle Aged; Aged
PubMed: 38677087
DOI: 10.1016/j.envint.2024.108665 -
Cancers Apr 2024(1) Background: -related schwannomatosis, characterized by the development of bilateral vestibular schwannomas, often necessitates varied treatment approaches....
(1) Background: -related schwannomatosis, characterized by the development of bilateral vestibular schwannomas, often necessitates varied treatment approaches. Bevacizumab, though widely utilized, demonstrates variable effectiveness on hearing and tumor growth. At the same time, (serious) adverse events have been frequently reported. (2) Methods: A single center retrospective study was conducted, on -related schwannomatosis patients treated with bevacizumab from 2013 to 2023, with the aim to assess treatment-related and clinical outcomes. Outcomes of interest comprised hearing, radiologic response, symptoms, and adverse events. (3) Results: Seventeen patients received 7.5 mg/kg bevacizumab for 7.1 months. Following treatment, 40% of the patients experienced hearing improvement, 53%, stable hearing, and 7%, hearing loss. Vestibular schwannoma regression occurred in 31%, and 69% remained stable. Further symptomatic improvement was reported by 41%, stable symptoms by 47%, and worsened symptoms by 12%. Treatment discontinuation due to adverse events was observed in 29% of cases. Hypertension (82%) and fatigue (29%) were most frequently reported, with no occurrences of grade 4/5 toxicities. (4) Conclusion: Supporting previous studies, bevacizumab demonstrated positive effects on hearing, tumor control, and symptoms in -related schwannomatosis, albeit with common adverse events. Therefore, careful consideration of an appropriate management strategy is warranted.
PubMed: 38672561
DOI: 10.3390/cancers16081479 -
Cureus Mar 2024Acoustic neuromas are benign neoplasms of the brain composed of Schwann cells, arising most commonly from the nerve sheath of the vestibular division of the VIII cranial...
Acoustic neuromas are benign neoplasms of the brain composed of Schwann cells, arising most commonly from the nerve sheath of the vestibular division of the VIII cranial nerve. They usually manifest as unilateral hearing loss, tinnitus, and unsteadiness. Some patients may present atypically with symptoms like orofacial pain, hemifacial numbness, sudden onset hearing loss, or trigeminal neuralgia. Here we report an interesting case of acoustic neuroma in which the patient presented with unilateral facial numbness and tooth pain. Persistent atypical symptoms should always raise clinical suspicion of this pathology, necessitating the need for higher radiological investigations (CT or MRI) to aid in the early diagnosis and treatment.
PubMed: 38650777
DOI: 10.7759/cureus.56745 -
Brain Tumor Pathology Apr 2024Ancient schwannoma (AS) is a subtype of schwannoma characterized by slow progression despite degenerative changes in pathology. Although it is considered a benign tumor,... (Comparative Study)
Comparative Study
Ancient schwannoma (AS) is a subtype of schwannoma characterized by slow progression despite degenerative changes in pathology. Although it is considered a benign tumor, most previous reports have focused on extracranial AS; therefore, the clinical characteristics of intracranial AS is not clear. We included 174 patients who underwent surgery for sporadic intracranial schwannoma, and 13 patients (7.5%) were diagnosed with AS. Cysts were significantly more common in patients with AS than conventional schwannomas (92.3% vs. 44.7%, p < 0.001), as was bleeding (38.5% vs. 6.9%, p = 0.003) and calcification (15.4% vs. 1.3%, p = 0.029). The maximum tumor diameter was also larger in patients with AS (35 mm vs. 29 mm, p = 0.017). The median duration from symptom onset to surgery (7.0 vs. 12.5 months, p = 0.740) did not significantly differ between groups, nor did the probability of postoperative recurrence (p = 0.949). Intracranial AS was strongly associated with cyst formation and exhibited a benign clinical course with a lower rate of recurrence and need for salvage treatment. Extracranial AS is reportedly characterized by a slow progression through a long-term clinical course, whereas intracranial AS did not progress slowly in our study and exhibited different clinical features to those reported for extracranial AS.
Topics: Adolescent; Adult; Aged; Female; Humans; Male; Middle Aged; Young Adult; Neurilemmoma; Neuroma, Acoustic; Radiology; Reproducibility of Results; Retrospective Studies
PubMed: 38578531
DOI: 10.1007/s10014-024-00482-z