| Abstract: |
Glioblastoma (GB) is the most aggressive primary brain tumor in adults, and its marked heterogeneity, diffuse infiltration, and a strongly immunosuppressive tumor microenvironment underlie the poor prognosis and near-inevitable relapses; temozolomide (TMZ) remains the backbone of standard therapy and can modulate antitumor immunity via immunogenic cell death (ICD), in which signals such as calreticulin (CRT) exposure and the release of ATP and High Mobility Group Box 1 (HMGB1) act as immune activators; in parallel, preclinical progress requires models that better recapitulate tumor physiology, and three-dimensional GL261 spheroids are proposed as an alternative to 2D monolayers, as they reproduce gradients, cell-cell contacts, and spatial heterogeneity, and this work contrasts the response to TMZ in 2D versus 3D, focusing on viability and immunogenicity; overall, the transition to 3D yields compact, viable spheroids and, considered together, 2D and 3D preparations show comparable susceptibility after longer exposures, with a slight tendency toward greater preservation of viability in 3D, attributable to gradients of drug penetration, oxygen, and nutrients; the ICD signals analyzed display modest, time-dependent changes: CRT exposure appears modest and transient, ATP tends to increase at early time points and decrease later, and HMGB1 may rise initially and decline as damage progresses; taken together, 3D confers biological value even with modest differences versus 2D and emerges as a useful platform for further optimization, and integrated evaluations (accounting for synergy among signals) with higher temporal resolution, along with the incorporation of additional immunogenic signals, could better capture relevant immunogenicity, moreover, preliminary internal observations suggest that implanted spheroids recapitulate in vivo features, reinforcing their translational potential. |
guest ::
dir. (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
