IT-20OVEREXPRESSION OF IL13Ra2: ASSESSMENT OF PRO-AGGRESSIVE AND PRO-INVASIVE PHENOTYPES OF MALIGNANT GLIOMA IN A SYNGENEIC ANIMAL MODEL

摘要

BACKGROUND: IL13Rα2 is a promising target for novel therapies in glioblastoma (GBM) due to its overexpression in tumor cells as well as glioma-initiating cells, which are responsible for the growth and recurrence of GBM. The role of IL13Ra2, found heterogeneously expressed in GBMs, is not fully understood and better targeting strategies are necessary for its clinical application. This study investigated the effectiveness of different patterns of IL13Rα2 expression on the survival of syngeneic rodent glioma models. This study also aims to act as a blueprint for further tests of the level of immune response to the target immunotherapy in immunocompetent mice bearing GBMs with different levels of IL13Rα2 expression. METHODS: G26 murine glioma cell line, with transfected to express hIL13Rα2 (G26-H2) and vector control (G26-V2) were intracranially injected in two groups of C57Bl/6 mice respectively. The metric analyzed for outcome was survival. Histological analysis were used to evaluate the level of IL13Ra2 expression in primary tissue obtained from patients with high gliomas. RESULTS: Two populations of G26 glioma cell lines were established per hIL13Rα2 expression: the hIL13Rα2⁺ and the hIL13Rα2⁻. In vivo, the cell lines showed a significant difference in survival: the group that received intracranial injection of G26-H2 cells (100% positive for hIL13Rα2) had a median survival of 29.5 days compared to 49 days for group receiving G26-V2 cells (100% negative for h IL13Rα2), p <0.0172. CONCLUSION: We assessed two different populations of G26 glioma cell lines: h IL13Rα2⁺ and h IL13Rα2⁻. In vivo, after intracranial implantation, the two populations showed a significant difference in survival. These results confirm the role of hIL13Rα2 overexpression in specific subtypes of GBMs, and most likely the most aggressive ones.