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

Sandén, Emma LU ; Enríquez Pérez, Julio LU ; Visse, Edward LU ; Kool, Marcel; Carén, Helena; Siesjö, Peter LU and Darabi, Anna LU (2016) In Pediatric Blood & Cancer 63(12). p.2112-2122
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cytokines, Multiplex immunoassay, Pediatric brain tumors, Systemic
in
Pediatric Blood & Cancer
volume
63
issue
12
pages
2112 - 2122
publisher
Wiley-Liss Inc.
external identifiers
  • scopus:84979735890
  • wos:000387023900007
ISSN
1545-5017
DOI
10.1002/pbc.26158
language
English
LU publication?
yes
id
cdd0200e-2fb9-4f87-9c43-b0b46f361c15
date added to LUP
2016-08-16 10:51:06
date last changed
2017-04-19 15:36:23
@article{cdd0200e-2fb9-4f87-9c43-b0b46f361c15,
  abstract     = {<p>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<sup>®</sup>). 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 VEGFA<sup>high</sup>IL-7<sup>high</sup>IL-17A<sup>low</sup>TNF-β<sup>low</sup> (Group A) and VEGFA<sup>low</sup>IL-7<sup>low</sup>IL-17A<sup>high</sup>TNF-β<sup>high</sup> (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.</p>},
  author       = {Sandén, Emma and Enríquez Pérez, Julio and Visse, Edward and Kool, Marcel and Carén, Helena and Siesjö, Peter and Darabi, Anna},
  issn         = {1545-5017},
  keyword      = {Cytokines,Multiplex immunoassay,Pediatric brain tumors,Systemic},
  language     = {eng},
  number       = {12},
  pages        = {2112--2122},
  publisher    = {Wiley-Liss Inc.},
  series       = {Pediatric Blood & Cancer},
  title        = {Preoperative systemic levels of VEGFA, IL-7, IL-17A, and TNF-β delineate two distinct groups of children with brain tumors},
  url          = {http://dx.doi.org/10.1002/pbc.26158},
  volume       = {63},
  year         = {2016},
}