Expansion of effector and memory T cells is associated with increased survival in recurrent glioblastomas treated with dendritic cell immunotherapy. Issue 1 (20th August 2019)

• Record Type: Journal Article
• Authors: Eoli, Marica; Corbetta, Cristina; Anghileri, Elena; Di Ianni, Natalia; Milani, Micaela; Cuccarini, Valeria; Musio, Silvia; Paterra, Rosina; Frigerio, Simona; Nava, Sara; Lisini, Daniela; Pessina, Sara; Maddaloni, Luisa; Lombardi, Raffaella; Tardini, Maria; Ferroli, Paolo; DiMeco, Francesco; Bruzzone, Maria Grazia; Antozzi, Carlo; Pollo, Bianca; Finocchiaro, Gaetano; Pellegatta, Serena
• Is Part Of: Neuro-oncology advances. Volume 1:Issue 1(2019)
• Publication Date: 2019-08-20
• Subjects: dendritic cells -- glioblastoma -- immunotherapy -- T-cell memory -- tetanus toxoid; 616.99481
• DOI: 10.1093/noajnl/vdz022
• Languages: English
• ISSNs: 2632-2498

Abstract

Abstract: Background: The efficacy of dendritic cell (DC) immunotherapy as a single therapeutic modality for the treatment of glioblastoma (GBM) patients remains limited. In this study, we evaluated in patients with GBM recurrence the immune-mediated effects of DC loaded with autologous tumor lysate combined with temozolomide (TMZ) or tetanus toxoid (TT). Methods: In the phase I-II clinical study DENDR2, 12 patients were treated with 5 DC vaccinations combined with dose-dense TMZ. Subsequently, in eight patients, here defined as Variant (V)-DENDR2, the vaccine site was preconditioned with TT 24 hours before DC vaccination and TMZ was avoided. As a survival endpoint for these studies, we considered overall survival 9 months (OS9) after second surgery. Patients were analyzed for the generation of effector, memory, and T helper immune response. Results: Four of 12 DENDR2 patients reached OS9, but all failed to show an immunological response. Five of eight V-DENDR2 patients (62%) reached OS9, and one patient is still alive (OS >30 months). A robust CD8 + T-cell activation and memory T-cell formation were observed in V-DENDR2 OS>9. Only in these patients, the vaccine-specific CD4 + T-cell activation (CD38 + /HLA-DR + ) was paralleled by an increase in TT-induced CD4 + /CD38 low /CD127 high memory T cells. Only V-DENDR2 patients showed the formation of a nodule at the DC injection site infiltrated by CCL3-expressing CD4 + T cells. Conclusions: TT preconditioning of the vaccine site and lack of TMZ could contribute to the efficacy of DC immunotherapy by inducing an effector response, memory, and helper T-cell generation.