Background Recovery following traumatic brain injury (TBI) is highly heterogeneous. Characterising longitudinal functional trajectories may enable more individualised care and inform the trial design. This study aimed to identify distinct patterns of functional recovery in the first 12 months post-injury using the Glasgow Outcome Scale – Extended (GOSE). Methods Patients with available GOSE data from Transforming Research and Clinical Knowledge in Traumatic Brain Injury, a prospective, multicentre study, were included. A two-stage multiple imputation procedure addressed missingness, and trajectories were modelled using polytomous variable latent class analysis (poLCA) in both complete-case and imputed datasets. Results Among the 2,100 participants with TBI, poLCA identified seven distinct recovery trajectories based on GOSE scores. These included (1) death (6.2%), (2) persistent GOSE 2–5 (5.7%), (3) improvement from GOSE 3–5 to GOSE 5 by 3 months with no further gains (9.0%), (4) rapid improvement from GOSE 3–5 to GOSE 7–8 sustained through follow-up (7.0%), (5) gradual improvement from GOSE 3–6 to GOSE 5–7 over 6 months (15.3%), (6) rapid early improvement from GOSE 4–7 to GOSE 6–8 by 3 months and then plateauing (21.8%) and (7) progression from GOSE 5–8 to GOSE 7–8 within 3 months, with stable outcomes thereafter (25.1%). Recovery class membership was significantly associated with the initial Glasgow Coma Scale scores, CT severity (Marshall and Rotterdam scores) and presence of psychiatric comorbidities. Conclusions Our findings support a shift towards trajectory-based stratification in clinical care and research. Incorporating these patterns into prognostic modelling may improve outcome prediction, personalise rehabilitation and refine eligibility criteria for interventional trials.

Inhibitory receptors are critical for regulating immune cell function. In cancer, these receptors are often over-expressed on the cell surface of T and NK cells, leading to reduced anti-tumor activity. Here, through the analysis of 11 commonly studied checkpoint and inhibitory receptors, we discern that only HAVCR2 (TIM3) and ENTPD1 (CD39) display significantly greater gene expression in glioblastoma compared to normal brain and lower grade glioma. Cell surface TIM-3, but not ENTPD1, was also elevated on activated CD4⁺ and CD8⁺ T cells, as well as on NK cells from glioblastoma patients compared to healthy donor T and NK cells. A subsequent analysis of molecules known to co-ordinate TIM-3 function and regulation was performed, which revealed that BAT3 expression was significantly reduced in CD4⁺ and CD8⁺ T cells, as well as NK cells from glioblastoma patients compared to counterparts from healthy donors. These pro-inhibitory changes are also correlated with reduced levels of the activation marker CD69 and the pro-inflammatory cytokine IFNγ in CD4⁺ and CD8⁺ T cells, as well as NK cells from glioblastoma patients. Collectively, these data reveal that glioblastoma-mediated CD4⁺ and CD8⁺ T cell and NK cell suppression is due, at least in part, to dysregulated TIM-3 and BAT3 expression and the associated downstream immunoregulatory and dysfunctional effects.

Glioblastoma is highly proliferative and invasive. However, the regulatory cytokine networks that promote glioblastoma cell proliferation and invasion into other areas of the brain are not fully defined. In the present study, we define a critical role for the IL-11/IL-11Rα signalling axis in glioblastoma proliferation, epithelial to mesenchymal transition, and invasion. We identified enhanced IL-11/IL-11Rα expression correlated with reduced overall survival in glioblastoma patients using TCGA datasets. Proteomic analysis of glioblastoma cell lines overexpressing IL-11Rα displayed a proteome that favoured enhanced proliferation and invasion. These cells also displayed greater proliferation and migration, while the knockdown of IL-11Rα reversed these tumourigenic characteristics. In addition, these IL-11Rα overexpressing cells displayed enhanced invasion in transwell invasion assays and in 3D spheroid invasion assays, while knockdown of IL-11Rα resulted in reduced invasion. Furthermore, IL-11Rα-overexpressing cells displayed a more mesenchymal-like phenotype compared to parental cells and expressed greater levels of the mesenchymal marker Vimentin. Overall, our study identified that the IL-11/IL-11Rα pathway promotes glioblastoma cell proliferation, EMT, and invasion.

Glioblastoma is the most aggressive primary brain malignancy, characterised by extensive intra-tumoural heterogeneity, therapy resistance, and a profoundly immunosuppressive tumour microenvironment. The galectin family, a group of β-galactoside-binding lectins, has emerged as a key regulator of tumour biology, influencing oncogenesis, immune modulation, and therapy resistance. In this study, we performed an integrative bioinformatics analysis to systematically evaluate the expression patterns, prognostic significance, genetic alterations, and functional roles of galectin family members in glioblastoma. We utilised publicly available genomic datasets and computational tools to perform our analysis, including UALCAN, GEPIA, cBioPortal, STRING, GeneMANIA, DAVID, and TIMER. We identified LGALS1, LGALS3, and LGALS9 as significantly upregulated in glioblastoma, with their overexpression correlating with adverse patient survival. Functional enrichment analysis highlighted galectin-mediated pathways involved in extracellular matrix remodelling, immune dysregulation, tumour-promoting pathways, and protein processing, suggesting their pivotal role in glioblastoma pathogenesis. We also show that transcriptional and immunological signatures suggest that galectins may regulate glioblastoma immunosuppression, extracellular matrix remodelling, and protein homeostasis. Our findings provide novel insights into the oncogenic and immunoregulatory roles of galectins in glioblastoma, establishing their potential as prognostic biomarkers and therapeutic targets.