Journal
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
Volume 76, Issue 9, Pages 779-788Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/jnen/nlx061
Keywords
Adamantinomatous craniopharyngioma; Craniopharyngioma cyst; Cytokine; IL-6; Immunomodulation; Inflammatory
Categories
Funding
- Morgan Adams Foundation
- Hartford Foundation for Public Giving
- Colorado Clinical and Translational Sciences Institute/Children's Hospital Colorado Research Institute [NCATS/NIH UL1 TR001082, NCI R03 CA212800-01]
- Medical Research Council MRC [M125/1]
- Children with Cancer UK CWCUK [15/190]
- National Institute of Health Research Biomedical Research Centre at Great Ormond Street Hospital
- University College London
- University of Colorado's NIH/NCI Cancer Center [P30CA046934]
- MRC [MR/M000125/1] Funding Source: UKRI
- Cancer Research UK [S_1731] Funding Source: researchfish
- Children with Cancer UK [15-190] Funding Source: researchfish
- Medical Research Council [MR/M000125/1] Funding Source: researchfish
- The Brain Tumour Charity [GN-000382] Funding Source: researchfish
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Pediatric adamantinomatous craniopharyngioma (ACP) is a highly solid and cystic tumor, often causing substantial damage to critical neuroendocrine structures such as the hypothalamus, pituitary gland, and optic apparatus. Paracrine signaling mechanisms driving tumor behavior have been hypothesized, with IL-6R overexpression identified as a potential therapeutic target. To identify potential novel therapies, we characterized inflammatory and immunomodulatory factors in ACP cyst fluid and solid tumor components. Cytometric bead analysis revealed a highly pro-inflammatory cytokine pattern in fluid from ACP compared to fluids from another cystic pediatric brain tumor, pilocytic astrocytoma. Cytokines and chemokines with particularly elevated concentrations in ACPs were IL-6, CXCL1 (GRO), CXCL8 (IL-8) and the immunosuppressive cytokine IL-10. These data were concordant with solid tumor compartment transcriptomic data from a larger cohort of ACPs, other pediatric brain tumors and normal brain. The majority of receptors for these cytokines and chemokines were also over-expressed in ACPs. In addition to IL-10, the established immunosuppressive factor IDO-1 was overexpressed by ACPs at the mRNA and protein levels. These data indicate that ACP cyst fluids and solid tumor components are characterized by an inflammatory cytokine and chemokine expression pattern. Further study regarding selective cytokine blockade may inform novel therapeutic interventions.
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