Inflammasome Activation in Glioblastoma Multiforme (P1.172)

Objective: The aim of this study was to define the expression of inflammasome-associated genes in glioblastoma multiforme (GBM). Background: GBM is the most prevalent and deadly adult brain cancer diagnosed worldwide, with a median survival of 15 months and a high rate of recurrence and resistance to therapeutic interventions. Inflammation is a key aspect of brain tumour biology, although it remains unclear how immune responses contribute to GBM pathogenesis or how these processes may be targeted therapeutically. Inflammasomes are intracellular multiprotein complexes that are activated by cellular stress and initiate the release of cytokines that might promote growth, angiogenesis, and immunological evasion in GBM. Design/Methods: Tissue samples from surgically-resected GBM tumours (n=10) were compared to age-and sex-matched Other Disease Control (ODC) samples from temporal lobectomies of patients with intractable epilepsy (n=7). Quantitative reverse-transcriptase PCR (qRT-PCR) was used to evaluate the expression of inflammasome and immunity-associated transcripts CASP1, IL1B, IL18, IL33, ASC, MX1, AIM2, NLRP3, NLRP1, NLRC4, CD3E, CD68, CD163, TNFA, and IFNG . Pharmacological induction of inflammasome transcripts in the human GBM cell line U251 was assessed in vitro. Results: GBM tumours showed elevated expression of NLRC4, AIM2, NLRP1 , and limited expression of IFNG and TNFA compared to ODC. CD68, ASC, NLRC4 , and IL1B transcripts were elevated in the periphery compared to the core of GBM tumours (p AIM2 was the only gene significantly elevated (p IL18 and could be induced to express NLRP3 and AIM2 with nigericin and hydrogen peroxide, respectively. Conclusions: This study identified an inflammasome expression profile in human GBM specimens that is unique from profiles observed in other inflammatory neurological diseases, such as multiple sclerosis and neurological infections. Study Supported by: Alberta Cancer Foundation Victor-Osten Summer Studentship Award Disclosure: Dr. Balcom has nothing to disclose. Dr. Branton has nothing to disclose. Dr. Petruk has nothing to disclose. Dr. Wheatley has nothing to disclose. Dr. van Landeghem has nothing to disclose. Dr. Power has nothing to disclose.