Preoperative systemic levels of VEGFA, IL-7, IL-17A, and TNF-β delineate two distinct groups of children with brain tumors

Research output: Contribution to journalArticle

Abstract

Background: 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. Procedure: 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. Results: 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. Conclusions: 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.

Details

Authors
Organisations
External organisations
  • German Cancer Research Centre
  • University of Gothenburg
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
  • Pediatrics

Keywords

  • Cytokines, Multiplex immunoassay, Pediatric brain tumors, Systemic
Original languageEnglish
Pages (from-to)2112-2122
JournalPediatric Blood & Cancer
Volume63
Issue number12
Early online date2016 Jul 29
Publication statusPublished - 2016 Dec
Publication categoryResearch
Peer-reviewedYes

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