Cytokines in Pediatric Pilocytic Astrocytomas: A Clinico-Pathological Study

Abstract

Pilocytic astrocytomas (PCA) are WHO Grade I tumors with a favorable prognosis. Surgical resection is usually curative. Nonetheless, progressive and/or metastatic disease occurs in 20% of patients. For these patients, treatment options are limited. The role of the immune system in PCA has not previously been reported. We hypothesize that the circulating cytokines contribute to tumorigenicity in PCA. This is an exploratory study with a focus on the identification of circulating cerebrospinal (CSF) cytokines associated with PCA. The primary objective is to demonstrate that CSF cytokines will be differentially expressed in the subset of PCAs that are difficult to treat in comparison to their surgically amendable counterparts. This is a single-institution, retrospective study of prospectively collected data. Patients with a confirmed histological diagnosis of PCA who have simultaneous intraoperative CSF sampling are included. Cerebrospinal fluid samples are subjected to multiplex cytokine profiling. Patient-derived PCA lines from selected patients in the same study cohort are cultured. Their cell culture supernatants are collected and interrogated using the sample multiplex platform as the CSF. A total of 8 patients are recruited. There were two patients with surgically difficult tumors associated with leptomeningeal involvement. Multiplex profiling of the cohort’s CSF samples showed elevated expressions of IFN-γ, IL-2, IL-12p70, IL-1β, IL-4, and TNF-α in these two patients in comparison to the remaining cohort. Next, primary cell lines derived from the same PCA patients demonstrated a similar trend of differential cytokine expression in their cell culture supernatant in vitro. Although our findings are preliminary at this stage, this is the first study in pediatric PCAs that show cytokine expression differences between the two groups of PCA with different clinical behaviors.

Immune Microenvironment in Childhood Cancers: Characteristics and Therapeutic Challenges

“…The study found that patients with ALL exhibit higher levels of a group of correlated cytokines, including IL-1β, IL-8, TNF-α, and VEGF, at birth compared to their healthy counterparts [ 92 ]. Similar cytokine profiling has been conducted in children with B-ALL, anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, pediatric pilocytic astrocytomas, as well as children with cancer and febrile neutropenia [ 93 , 94 , 95 , 96 ]. These findings collectively suggest an intriguing association between cytokine levels and tumor development.…”