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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

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

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  • Media type: E-Article
  • Title: Expansion of effector and memory T cells is associated with increased survival in recurrent glioblastomas treated with dendritic cell immunotherapy
  • Contributor: 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
  • imprint: Oxford University Press (OUP), 2019
  • Published in: Neuro-Oncology Advances
  • Language: English
  • DOI: 10.1093/noajnl/vdz022
  • ISSN: 2632-2498
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>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).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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 &amp;gt;30 months). A robust CD8+ T-cell activation and memory T-cell formation were observed in V-DENDR2 OS&amp;gt;9. Only in these patients, the vaccine-specific CD4+ T-cell activation (CD38+/HLA-DR+) was paralleled by an increase in TT-induced CD4+/CD38low/CD127high 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.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p> </jats:sec>
  • Access State: Open Access