Enhancing anti-EGFRvIII CAR T cell therapy against glioblastoma with a paracrine SIRPγ-derived CD47 blocker.

A significant challenge for chimeric antigen receptor (CAR) T cell therapy against glioblastoma (GBM) is its immunosuppressive microenvironment, which is densely populated by protumoral glioma-associated microglia and macrophages (GAMs). Myeloid immune checkpoint therapy targeting the CD47-signal regulatory protein alpha (SIRPα) axis induces GAM phagocytic function, but CD47 blockade monotherapy is associated with toxicity and low bioavailability in solid tumors. In this work, we engineer a CAR T cell against epidermal growth factor receptor variant III (EGFRvIII), constitutively secreting a signal regulatory protein gamma-related protein (SGRP) with high affinity to CD47.

Endovascular Treatment and Peri-interventional Management of Ruptured Cerebrovascular Lesions During Pregnancy : Case Series and Case-based Systematic Review.

Purpose: Hemorrhagic stroke, particularly occurring from ruptured cerebrovascular malformations, is responsible for 5-12% of all maternal deaths during pregnancy and the puerperium. Whether endovascular treatment is feasible and safe for both the mother and the fetus, is still a matter of debate. The main objective of this case series and systematic review was to share our multi-institutional experience and to assess the feasibility and safety of endovascular treatment during pregnancy, as well as the corresponding maternal and fetal outcomes based on currently available evidence.

Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study.

Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes.

Brain cortical alterations in COVID-19 patients with neurological symptoms.

Background: Growing evidence suggests that the central nervous system is affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), since infected patients suffer from acute and long-term neurological sequelae. Nevertheless, it is currently unknown whether the virus affects the brain cortex. The purpose of this study was to assess the cortical gray matter volume, the cortical thickness, and the cortical surface area in a group of SARS-CoV-2 infected patients with neurological symptoms compared to healthy control subjects.

Immunotherapy of glioblastoma explants induces interferon-γ responses and spatial immune cell rearrangements in tumor center, but not periphery.

A patient-tailored, ex vivo drug response platform for glioblastoma (GBM) would facilitate therapy planning, provide insights into treatment-induced mechanisms in the immune tumor microenvironment (iTME), and enable the discovery of biomarkers of response. We cultured regionally annotated GBM explants in perfusion bioreactors to assess iTME responses to immunotherapy. Explants were treated with anti-CD47, anti-PD-1, or their combination, and analyzed by multiplexed microscopy [CO-Detection by indEXing (CODEX)], enabling the spatially resolved identification of >850,000 single cells, accompanied by explant secretome interrogation.

Treatment and Postinterventional Management of a Fusiform Intracranial Aneurysm in a Professional Soccer Player: A Case Report.

Introduction: While intracranial aneurysms are common lesions affecting between 1 and 5% of the general population, the prevalence in professional athletes remains unknown. The result is uncertainty and lack of guidelines on appropriate treatment of these patients.

Case Presentation: A 29-year-old professional soccer player presented in our hospital with an incidentally found intracranial aneurysm.