Tertiary lymphoid structures (TLS) classification: a new perspective on glioblastoma patient’s prognosis

Tertiary lymphoid structures (TLS) are pivotal modulators of anti-tumor immunity in solid tumors; however, their clinical significance in glioblastoma (GBM) remains under-characterized. This study aimed to evaluate the correlation between TLS spatial-quantitative characteristics and survival outcomes in GBM patients to refine prognostic stratification and immunotherapy optimization. A retrospective analysis was conducted on 62 patients with isocitrate dehydrogenase (IDH)-wildtype GBM treated at our institution (2016 – 2023). TLSs were identified via H&E and CD3 / CD20 immunohistochemical (IHC) staining. A grading system was established based on the quantity and spatial distribution (intratumoral vs. peritumoral) of TLS. Survival outcomes were assessed using Kaplan–Meier curves and multivariate Cox regression models to identify independent prognostic factors. TLSs were present in 58.1% of the cohort. Survival analysis revealed that TLS status, grading, and extent of resection significantly correlated with overall survival (OS; P < 0.05). Notably, higher TLS grades, particularly those characterized by intratumoral localization (Score 3), were associated with significantly prolonged OS. Multivariate analysis confirmed that TLS grading is an independent favorable prognostic factor for OS in this GBM cohort. The proposed TLS grading system provides a potential prognostic stratification tool for GBM that warrants external validation. These findings emphasize the role of TLSs in the GBM immune microenvironment and offer a potential biomarker for selecting patients likely to benefit from intensified immunotherapeutic interventions.