TMIC-28. TITLE: AN IMMUNE-RELATED, SEX-SPECIFIC T-CELL SIGNATURE IN GLIOBLASTOMA MICROENVIRONMENT WITH PROGNOSTIC IMPACT

Abstract BACKGROUND Glioblastoma, IDH-wildtype (GBM), is the most prevalent and aggressive primary brain cancer with a poor prognosis. Immune checkpoint inhibitors (ICIs) have been explored in GBM with limited success, highlighting the need for a better understanding of the tumor microenvironment (TME). This study investigated whether the expression of specific immune checkpoints on tissue-resident memory T cells (Trm) predicts patient outcomes. METHODS In a single cohort observational study, tumor samples from 45 histologically confirmed GBM patients were processed to obtain single-cell suspensions. Multiparametric flow cytometry was used to analyze the correlation of Trm phenotypes with overall survival (OS) and progression-free survival (PFS). Univariate and multivariate analyses were conducted to assess the prognostic significance of Trm subsets. RESULTS Low frequency of exausted Trm expressing programmed cell death protein 1 (PD1) and T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) was associated with better clinical outcomes. Multivariate analysis identified low CD8+CD103+PD1+TIM3+ Trm and Karnofsky performance status (KPS) ≥70 as the most significant independent prognostic factors for longer OS (hazard ratios—HR [95%CI]: 0.14 [0.04–0.52] p < 0.001, 0.39 [0.16–0.96] p = 0.04, respectively). Additionally, younger patients (<63 years) and males had distinct immune profiles affecting prognosis. Notably, the proportion of exausted CD8+CD103+PD1+ Trms had a prognostic correlate only in male patients, consistent with findings by other groups on the existance of gender-specific immune TME in GBM. CONCLUSIONS Further exploration of Trm-based immune profiling has the potential to shed light on GBM resistance to ICIs and to help in personalizing treatment strategies.