GLIO_IL-23 · EFFECT OF IL-23 ON IMMUNE CELL INFILTRATION AND TUMOR GROWTH IN A GLIOMA MODEL

Malignant gliomas are the most common primary central nervous system (CNS) tumors in humans and belong to the most aggressive types of cancer. Glioblastoma cells display an invasive phenotype and release immunosuppressive molecules to avoid the host’s immune response. Therefore, there is an urgent need for novel tumor-selective treatments that specifically target migratory glioma cells and/or promote inflammatory anti-tumor responses.The possibility of using immuno-therapy to control tumor growth is currently being investigated. Considering the CNS, this approach acquires unique characteristics due mainly to the existence of the blood brain barrier. In this regard, the IL-12/IL-23 superfamily of cytokines represents a promising immuno-therapy tool. Despite their structural similarities, they play different roles in the immune response promoting Th1 or Th17 polarization, respectively. Moreover, IL-23 but not IL-12 has been described as essential for the infiltration of CD4+ cells into the CNS in experimental autoimmune encephalomyelitis (EAE). Considering tumor growth, the anti-tumoral effects of IL-12 have been described in several models including glioma. However, in the case of IL-23 both tumor-promoting and tumor-suppressive effects have been reported, depending if endogenous or exogenous IL-23 is examined. Regarding glioma models, no data is available on how endogenous IL-23 may modulate tumor growth.The goal of this project is to evaluate the differences of endogenous and exogenous IL-23 effect on a glioma model. Moreover, the possible modulation exerted by IL-23 on immune cell infiltration into the CNS in a glioma context will be studied. To achieve these objectives, novel multimodal non-invasive molecular imaging techniques will be used, providing not only spatio-temporal information but also quantitative data regarding tumor growth, matrix-metalloproteinase activity and immune cell infiltration into the CNS.""