Remote Neuroinflammation in Newly Diagnosed Glioblastoma Correlates with Unfavorable Clinical Outcome

Abstract

AbstractLocal therapy strategies still provide only limited success in the treatment of glioblastoma, the most frequent primary brain tumor in adults, indicating global involvement of the brain in this fatal disease. To study the impact of neuroinflammation distant of the primary tumor site on the clinical course of patients with glioblastoma, we performed translocator protein (TSPO)-PET in patients with newly diagnosed glioblastoma, glioma WHO 2 and healthy controls and compared signals of the non-lesion (i.e. contralateral) hemisphere. Back-translation in syngeneic glioblastoma mice was used to characterize PET alterations on a cellular level. Ultimately, multiplex gene expression analyses served to profile immune cells in remote brain. Our study revealed elevated TSPO-PET signals in contralateral hemispheres of patients with newly diagnosed glioblastoma compared to healthy controls. Contralateral TSPO was associated with persisting epilepsy and short survival independent of the tumor phenotype. Back-translation pinpointed myeloid cells as the source of TSPO-PET signal increases and revealed a complex immune signature comprised of joint myeloid cell activation and immunosuppression in distant brain regions. In brief, neuroinflammation within the contralateral hemisphere is associated with poor outcome in patients with newly diagnosed glioblastoma. TSPO-PET serves to detect patients with global neuroinflammation who may benefit from immunomodulatory strategies.