Preoperative systemic levels of VEGFA, IL‐7, IL‐17A, and TNF‐β delineate two distinct groups of children with brain tumors. Issue 12 (29th July 2016)

• Record Type: Journal Article
• Authors: Sandén, Emma; Enríquez Pérez, Julio; Visse, Edward; Kool, Marcel; Carén, Helena; Siesjö, Peter; Darabi, Anna
• Is Part Of: Pediatric blood & cancer. Volume 63:Issue 12(2016)
• Page Start: 2112
• Page End: 2122
• Publication Date: 2016-07-29
• Subjects: cytokines -- multiplex immunoassay -- pediatric brain tumors -- systemic; Tumors in children -- Periodicals; Blood -- Diseases -- Periodicals; Cancer in children -- Periodicals; 618.92
• DOI: 10.1002/pbc.26158
• Languages: English
• ISSNs: 1545-5009

Abstract

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 VEGFA high IL‐7 high IL‐17A low TNF‐β low (Group A) and VEGFA low IL‐7 low IL‐17A high TNF‐β 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‐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.