title: Preoperative systemic levels of VEGFA, IL-7, IL-17A, and TNF-β delineate two distinct groups of children with brain tumors.
abstract: Primary brain tumors are the most common solid tumors in children. Increasing evidence demonstrates diverse intratumoral immune signatures, which are tentatively reflected in peripheral blood.
  
  
  
  Twenty cytokines were analyzed in preoperative plasma samples from five healthy children and 45 children with brain tumors, using a multiplex platform (MesoScale Discovery V-PLEX®). Tumor types included medulloblastoma (MB), ependymoma, sarcoma, high-grade glioma, pilocytic astrocytoma, and other low-grade gliomas.
  
  
  
  A panel of four cytokines [VEGFA, interleukin (IL)-7, IL-17A, and tumor necrosis factor (TNF)-β] delineated two distinct patient groups, identified as VEGFAhighIL-7highIL-17AlowTNF-βlow(Group A) and VEGFAlowIL-7lowIL-17AhighTNF-βhigh(Group B). Healthy controls and the vast majority of patients with MB were found within Group A, whereas patients with other tumor types were equally distributed between the two groups. Unrelated to A/B affiliation, we detected trends toward increased IL-10 and decreased IL-12/23 and TNF-α in several tumor types. Finally, a small number of patients displayed evidence of enhanced systemic immune activation, including elevated levels of interferon-γ, granulocyte monocyte colony-stimulating factor, IL-6, IL-12/23, and TNF-α. Following tumor resection, cytokine levels in a MB patient approached the levels of healthy controls.
  
  
  
  We identify common features and individual differences in the systemic immune profiles of children with brain tumors. Overall, patients with MB displayed a uniform cytokine profile, whereas other tumor diagnoses did not predict systemic immunological status in single patients. Future characterization and monitoring of systemic immune responses in children with brain tumors will have important implications for the development and implementation of immunotherapy.
authors.affiliation: Glioma Immunotherapy Group, Faculty of Medicine, Department of Clinical Sciences Lund, Neurosurgery, Lund University, Lund, Sweden. Emma.Sanden@med.lu.se.
authors.forename: Emma
authors.initials: E
authors.lastname: Sandén
authors.affiliation: Glioma Immunotherapy Group, Faculty of Medicine, Department of Clinical Sciences Lund, Neurosurgery, Lund University, Lund, Sweden.
authors.forename: Julio
authors.initials: J
authors.lastname: Enríquez Pérez
authors.affiliation: Glioma Immunotherapy Group, Faculty of Medicine, Department of Clinical Sciences Lund, Neurosurgery, Lund University, Lund, Sweden.
authors.forename: Edward
authors.initials: E
authors.lastname: Visse
authors.affiliation: Division of Pediatric Neurooncology, German Cancer Research Center DKFZ, Heidelberg, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kool
authors.affiliation: Sahlgrenska Cancer Center, Department of Pathology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Carén
authors.affiliation: Glioma Immunotherapy Group, Faculty of Medicine, Department of Clinical Sciences Lund, Neurosurgery, Lund University, Lund, Sweden.|Department of Clinical Sciences Lund, Neurosurgery, Lund University, Skåne University Hospital, Lund, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Siesjö
authors.affiliation: Glioma Immunotherapy Group, Faculty of Medicine, Department of Clinical Sciences Lund, Neurosurgery, Lund University, Lund, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Darabi
mesh_terms: D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000276:immunology* / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000097:blood*; D015851:Interleukin-7 / Q000097:blood*; D008233:Lymphotoxin-alpha / Q000097:blood*; D008297:Male; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17; D015851:Interleukin-7; D008233:Lymphotoxin-alpha; D042461:Vascular Endothelial Growth Factor A
keywords: cytokines; multiplex immunoassay; pediatric brain tumors; systemic