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

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 VEGFAhigh IL-7high IL-17Alow TNF-βlow (Group A) and VEGFAlow IL-7low IL-17Ahigh TNF-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.

• Authors: Emma Sandén, Julio Enríquez Pérez, Edward Visse, Marcel Kool, Helena Carén, Peter Siesjö, Anna Darabi
• Journal: Pediatric blood & cancer (Pediatr Blood Cancer) Vol. 63 Issue 12 Pg. 2112-2122 (12 2016) ISSN: 1545-5017 [Electronic] United States
• PMID: 27472224 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 Wiley Periodicals, Inc.

Chemical References

• IL17A protein, human
• Interleukin-17
• Interleukin-7
• Lymphotoxin-alpha
• Vascular Endothelial Growth Factor A

Topics

• Adolescent
• Adult
• Brain Neoplasms (immunology, surgery)
• Child
• Child, Preschool
• Female
• Humans
• Interleukin-17 (blood)
• Interleukin-7 (blood)
• Lymphotoxin-alpha (blood)
• Male
• Vascular Endothelial Growth Factor A (blood)