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

Pellegatta, S., Eoli, M., Cuccarini, V., Anghileri, E., Pollo, B., Pessina, S., et al. (2018). 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, 7(4) [10.1080/2162402X.2017.1412901].

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

Pellegatta, Serena
Primo
;
Pessina, Sara;Cuppini, Lucia;CUZZUBBO, STEFANIA;CORBETTA, CRISTINA;
2018

Abstract

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
Articolo in rivista - Articolo scientifico
adjuvant chemotherapy; dendritic cells; Glioblastoma; immunotherapy; natural killer cells; Immunology and Allergy; Immunology; Oncology
English
2018
7
4
e1412901
none
Pellegatta, S., Eoli, M., Cuccarini, V., Anghileri, E., Pollo, B., Pessina, S., et al. (2018). 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, 7(4) [10.1080/2162402X.2017.1412901].
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/205346
Citazioni
  • Scopus 51
  • ???jsp.display-item.citation.isi??? 50
Social impact