PERSISTENT EXPRESSION OF CHITINASE 3-LIKE 1 IN EX VIVO-MAINTAINED GLIOBLASTOMA BIOPSIES DESPITE CHEMOTHERAPY: IMPLICATIONS FOR IMMUNE EVASION

Abstract AIMS Background: Glioblastoma (GBM) remains a highly aggressive and treatment-resistant brain tumour, characterized by pro- found immune suppression. Chitinase 3-like 1 (CHI3L1), a cytokine implicated in tumour progression and im- mune modulation, has been associated with poor prognosis in GBM. This study examines CHI3L1 expression in ex vivoGBM tissue maintained on a microfluidic platform, investigating changes on application of standard-of- care chemotherapy. AIMS To assess CHI3L1 secretion in patient-derived GBM tissue under physiological perfusion conditions and deter- mine its response to clinically relevant chemotherapeutic agents. METHODS GBM biopsy samples from 13 patients were cultured on a microfluidic perfusion system for 8-12 days. Tissue was either maintained untreated or exposed to a combination of Temozolomide (TMZ) and a PRMT inhibitor. CHI3L1 levels were quantified using a Proteome Profiler Human XL Cytokine Array and validated via ELISA. CONCLUSION The persistence and upregulation of CHI3L1 in treated GBM tissue highlights a potential role in immune eva- sion and/or therapeutic resistance. These findings suggest that targeting CHI3L1 could enhance the efficacy of current GBM treatments and improve patient outcomes; further clinical investigations are required.