Expansion of effector and memory T cells is associated with increased survival in recurrent glioblastomas treated with dendritic cell immunotherapy

• Published in: Neuro-oncology advances Vol. 1; no. 1; p. vdz022
• Main 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
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.05.2019
• Subjects: Clinical Investigations; dendritic cells; glioblastoma; T-cell memory; tetanus toxoid; immunotherapy
• ISSN: 2632-2498; 2632-2498
• DOI: 10.1093/noajnl/vdz022

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). 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. 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 /CD127 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. 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.