Abstract
BACKGROUND
Despite the first classification of glioblastoma as an immunologically “cold” tumor, accumulating evidence suggests that this cancer type is susceptible to T cell infiltration, providing a glimmer of hope for the development of effective immunotherapy approaches that until now had limited success in brain tumors. To explore the contribution of biomarkers that could identify groups of patients showing durable response to immunotherapy, we examined several clinical and biological finding in 69 newly-diagnosed glioblastoma patients treated with dendritic cell (DC) immunotherapy added to standard treatment (DENDR1 NCT04801147).
MATERIAL AND METHODS
Patients with post-surgery volume ≤10 cc underwent leukapheresis before radiotherapy and chemotherapy with temozolomide (TMZ). Three intradermal injections of mature DC loaded with whole tumor lysate were administrated before and four after adjuvant TMZ. In all patients peripheral immune effector subsets were assessed including T and NK cells,, In all tumor samples MGMT methylation status was evaluated, and in 36 cases an immunohistochemistry (IHC) analysis was performed on tumor specimen collected before DC immunotherapy.
RESULTS
After a median follow-up of 23months (mo) median progression-free survival (PFS) was 12 mo (CI 95%10.34-13.6) and median overall
survival (OS) was 22.6 mo (CI 95%18.7-24.5) comparing favorably with OS expected from the literature. MGMT status and expansion of NK cells positively impacted PFS and OS. Furthermore, our preliminary results suggest an association between the density and localization of specific Tumor Infiltrating Lymphocytes (TILs) and patients’ response to immunotherapy. TIL spatial patterns revealed either an immune-excluded, or an immune-infiltrated scenario with either scattered, clustered, or widespread T cell infiltration. Notably, an abundant widespread infiltration of CD8 TILs was correlated with prolonged survival of DENDR1 patients (PFS 18.0 vs. 8.9; OS 33.6 vs. 11.0; p< 0.005 compared with excluded CD8+ TIL distribution), supporting that distribution can be predictive of immunotherapy responsiveness.
CONCLUSION
These findings suggest that in DENDR-1 improved clinical outcomes correlate with an increase in the number of active NK cells, MGMT status, and abundant widespread infiltration of CD8+ TILs.