Search

Abstract Current treatment outcome of patients with glioblastoma (GBM) remains poor. Following standard therapy, recurrence is universal with limited survival. Tumors from 173 GBM patients are analysed for somatic mutations to generate a personalized peptide vaccine targeting tumor-specific neoantigens. All patients were treated within the scope of an individual healing attempt. Among all vaccinated patients, including 70 treated prior to progression (primary) and 103 treated after progression (recurrent), the median overall survival from first diagnosis is 31.9 months (95% CI: 25.0–36.5). Adverse events are infrequent and are predominantly grade 1 or 2. A vaccine-induced immune response to at least one of the vaccinated peptides is detected in blood samples of 87 of 97 (90%) monitored patients. Vaccine-specific T-cell responses are durable in most patients. Significantly prolonged survival is observed for patients with multiple vaccine-induced T-cell responses (53 months) compared to those with no/low induced responses (27 months; P = 0.03). Altogether, our results highlight that the application of personalized neoantigen-targeting peptide vaccine is feasible and represents a promising potential treatment option for GBM patients.

Abstract Brown and brown-like adipose tissues have attracted significant attention for their role in metabolism and therapeutic potential in diabetes and obesity. Despite compelling evidence of an interplay between adipocytes and lymphocytes, the involvement of these tissues in immune responses remains largely unexplored. This study explicates a newfound connection between neuroinflammation and brown- and bone marrow adipose tissue. Leveraging the use of [18F]F-AraG, a mitochondrial metabolic tracer capable of tracking activated lymphocytes and adipocytes simultaneously, we demonstrate, in models of glioblastoma and multiple sclerosis, the correlation between intracerebral immune infiltration and changes in brown- and bone marrow adipose tissue. Significantly, we show initial evidence that a neuroinflammation-adipose tissue link may also exist in humans. This study proposes the concept of an intricate immuno-neuro-adipose circuit, and highlights brown- and bone marrow adipose tissue as an intermediary in the communication between the immune and nervous systems. Understanding the interconnectedness within this circuitry may lead to advancements in the treatment and management of various conditions, including cancer, neurodegenerative diseases and metabolic disorders.

Intrinsic, expansile pontine tumors typically occur in the pediatric population. These tumors characteristically present as diffuse intrinsic pontine glioma (DIPG), which is now considered as diffuse midline glioma (DMG), H3K27-mutated of the pons. DIPG has limited treatment options and a poor prognosis, and the value of tissue diagnosis from an invasive biopsy remains controversial. This study presents the case of a 19-year-old female with clinical and imaging hallmarks of DIPG, who underwent a biopsy of a tumor in the region of the right middle cerebellar peduncle. Her lesional cells were negative for H3K27M alterations and had low-grade histologic features. Next-generation sequencing revealed a frameshift mutation in the NF1 gene as the likely driver mutation. These features suggest a diagnosis of a low-grade glioma associated with NF1 loss of function, with far-reaching consequences regarding both treatment strategy and prognosis. This case provides support for the utility of diagnostic tissue biopsy in cases of suspected DIPG.

Introduction and background: While recurrent glioblastoma patients are often treated with re-irradiation, there is limited data on the use of re-irradiation in the setting of bevacizumab (BEV), temozolomide (TMZ) re-challenge, or immune checkpoint inhibition (ICI). We describe target delineation in patients with prior anti-angiogenic therapy, assess safety and efficacy of re-irradiation, and evaluate patterns of recurrence. Materials and methods: Patients with a histologically confirmed diagnosis of glioblastoma treated at a single institution between 2013 and 2021 with re-irradiation were included. Tumor, treatment and clinical data were collected. Logistic and Cox regression analysis were used for statistical analysis. Results: One hundred and seventeen recurrent glioblastoma patients were identified, receiving 129 courses of re-irradiation. In 66 % (85/129) of cases, patients had prior BEV. In the 80 patients (62 %) with available re-irradiation plans, 20 (25 %) had all T2/FLAIR abnormality included in the gross tumor volume (GTV). Median overall survival (OS) for the cohort was 7.3 months, and median progression-free survival (PFS) was 3.6 months. Acute CTCAE grade ≥ 3 toxicity occurred in 8 % of cases. Concurrent use of TMZ or ICI was not associated with improved OS nor PFS. On multivariable analysis, higher KPS was significantly associated with longer OS (p

Objective: There is emerging evidence suggesting that pregnancy loss (induced or natural) is associated with an increased risk of cardiovascular diseases (CVD). This prospective longitudinal study investigates the effect of prior pregnancy losses on CVD risk during the first six months following a first live birth. Methods: Medicaid claims of 1,002,556 low-income women were examined to identify history of pregnancy losses, CVD, diabetes, and hyperlipidemia prior to first live birth. The study population was categorized into five groups: A: women with no pregnancy loss or CVD history prior to first live birth; B: women with pregnancy loss and no CVD prior to first live birth. C: women with a first CVD diagnosis after a first pregnancy ending in a loss and before their first live birth. D: women with CVD prior to first live birth and no history of pregnancy loss. E: women with both CVD and pregnancy loss prior to their first live birth. Results: After controlling for age, race, state of residence, and history of diabetes and hyperlipidemia, the risk of CVD in the six-month period following a first live birth were 15%, 214%, 79% and 129% more common for Groups B, C, D and E, respectively, compared to Group A. Conclusions: Pregnancy loss is an independent risk factor for CVD risk following a first live birth, both for women with and without a prior history of CVD. The risk is highest when CVD is first diagnosed after a pregnancy loss and prior to a first live birth.