Survival gain in glioblastoma patients treated with dendritic cell immunotherapy is associated with increased NK but not CD8+ T cell activation in the presence of adjuvant temozolomide

OncoImmunology

Simona Frigerio¹  Eugenio A. Parati¹  Lucia Cuppini²  Rosina Paterra²  Stefania Cuzzubbo²  Serena Pellegatta²  Marica Eoli²  Elena Anghileri²  Sara Pessina²  Maura Servida²  Cristina Corbetta²  Gaetano Finocchiaro²  Carlo Antozzi³  Valeria Cuccarini⁴  Maria Grazia Bruzzone⁴  Bianca Pollo⁵  Francesco DiMeco⁶  Paolo Ferroli⁷  Francesco Acerbi⁷  Laura Fariselli⁸ 

[1] Cell Therapy Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta;Unit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta;Unit of Neuro-Immunology, Fondazione IRCCS Istituto Neurologico Carlo Besta;Unit of Neuro-Radiology, Fondazione IRCCS Istituto Neurologico Carlo Besta;Unit of Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta;Unit of Neurosurgery 1, Fondazione IRCCS Istituto Neurologico Carlo Besta;Unit of Neurosurgery 2, Fondazione IRCCS Istituto Neurologico Carlo Besta;Unit of Radiotherapy, Fondazione IRCCS Istituto Neurologico Carlo Besta;

关键词: glioblastoma;    dendritic cells;    immunotherapy;    adjuvant chemotherapy;    natural killer cells;   

DOI  :  10.1080/2162402X.2017.1412901

来源: DOAJ

【 摘 要 】

In a two-stage phase II study, 24 patients with first diagnosis of glioblastoma (GBM) were treated with dendritic cell (DC) immunotherapy associated to standard radiochemotherapy with temozolomide (TMZ) followed by adjuvant TMZ. Three intradermal injections of mature DC loaded with autologous GBM lysate were administered before adjuvant TMZ, while 4 injections were performed during adjuvant TMZ. According to a two-stage Simon design, to proceed to the second stage progression-free survival (PFS) 12 months after surgery was expected in at least 8 cases enrolled in the first stage. Evidence of immune response and interaction with chemotherapy were investigated. After a median follow up of 17.4 months, 9 patients reached PFS12. In these patients (responders, 37.5%), DC vaccination induced a significant, persistent activation of NK cells, whose increased response was significantly associated with prolonged survival. CD8+ T cells underwent rapid expansion and priming but, after the first administration of adjuvant TMZ, failed to generate a memory status. Resistance to TMZ was associated with robust expression of the multidrug resistance protein ABCC3 in NK but not CD8+ T cells. The negative effect of TMZ on the formation of T cell-associated antitumor memory deserves consideration in future clinical trials including immunotherapy.

【 授权许可】

Unknown