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

Artikel i vetenskaplig tidskrift
Författare E. Sanden
J. E. Perez
E. Visse
M. Kool
Helena Carén
P. Siesjo
A. Darabi
Publicerad i Pediatr Blood Cancer
Volym 63
Nummer/häfte 12
Sidor 2112-2122
ISSN 1545-5009
Publiceringsår 2016
Publicerad vid Sahlgrenska Cancer Center
Institutionen för biomedicin, avdelningen för patologi
Sidor 2112-2122
Språk en
Ämnesord cytokines, multiplex immunoassay, pediatric brain tumors, systemic, encephalomyelitis/chronic fatigue syndrome, posterior-fossa ependymoma, glioblastoma patients, immune gene, cells, expression, medulloblastoma, methylation, astrocytoma, glioma, Oncology, Hematology, Pediatrics
Ämneskategorier Klinisk medicin

Sammanfattning

BackgroundPrimary brain tumors are the most common solid tumors in children. Increasing evidence demonstrates diverse intratumoral immune signatures, which are tentatively reflected in peripheral blood. ProcedureTwenty 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 (R)). Tumor types included medulloblastoma (MB), ependymoma, sarcoma, high-grade glioma, pilocytic astrocytoma, and other low-grade gliomas. ResultsA panel of four cytokines [VEGFA, interleukin (IL)-7, IL-17A, and tumor necrosis factor (TNF)-] delineated two distinct patient groups, identified as VEGFA(high)IL-7(high)IL-17A(low)TNF-(low) (Group A) and VEGFA(low)IL-7(low)IL-17A(high)TNF-(high) (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- in several tumor types. Finally, a small number of patients displayed evidence of enhanced systemic immune activation, including elevated levels of interferon-, granulocyte monocyte colony-stimulating factor, IL-6, IL-12/23, and TNF-. Following tumor resection, cytokine levels in a MB patient approached the levels of healthy controls. ConclusionsWe 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.

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