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

Emma Sandén, Julio Enríquez Pérez, Edward Visse, Marcel Kool, Helena Carén, Peter Siesjö, Anna Darabi

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

14 Citaten (Scopus)


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.

Originele taal-2Engels
Pagina's (van-tot)2112-2122
Aantal pagina's11
TijdschriftPediatric Blood and Cancer
Nummer van het tijdschrift12
StatusGepubliceerd - 1 dec. 2016
Extern gepubliceerdJa


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