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.
| Original language | English |
|---|---|
| Article number | e1412901 |
| Journal | OncoImmunology |
| Volume | 7 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 3 2018 |
Fingerprint
Keywords
- adjuvant chemotherapy
- dendritic cells
- Glioblastoma
- immunotherapy
- natural killer cells
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Oncology
Cite this
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; Eoli, Marica; Cuccarini, Valeria; Anghileri, Elena; Pollo, Bianca; Pessina, Sara; Frigerio, Simona; Servida, Maura; Cuppini, Lucia; Antozzi, Carlo; Cuzzubbo, Stefania; Corbetta, Cristina; Paterra, Rosina; Acerbi, Francesco; Ferroli, Paolo; DiMeco, Francesco; Fariselli, Laura; Parati, Eugenio A.; Bruzzone, Maria Grazia; Finocchiaro, Gaetano.
In: OncoImmunology, Vol. 7, No. 4, e1412901, 03.04.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Pellegatta, Serena
AU - Eoli, Marica
AU - Cuccarini, Valeria
AU - Anghileri, Elena
AU - Pollo, Bianca
AU - Pessina, Sara
AU - Frigerio, Simona
AU - Servida, Maura
AU - Cuppini, Lucia
AU - Antozzi, Carlo
AU - Cuzzubbo, Stefania
AU - Corbetta, Cristina
AU - Paterra, Rosina
AU - Acerbi, Francesco
AU - Ferroli, Paolo
AU - DiMeco, Francesco
AU - Fariselli, Laura
AU - Parati, Eugenio A.
AU - Bruzzone, Maria Grazia
AU - Finocchiaro, Gaetano
PY - 2018/4/3
Y1 - 2018/4/3
N2 - 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.
AB - 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.
KW - adjuvant chemotherapy
KW - dendritic cells
KW - Glioblastoma
KW - immunotherapy
KW - natural killer cells
UR - http://www.scopus.com/inward/record.url?scp=85041205360&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85041205360&partnerID=8YFLogxK
U2 - 10.1080/2162402X.2017.1412901
DO - 10.1080/2162402X.2017.1412901
M3 - Article
AN - SCOPUS:85041205360
VL - 7
JO - OncoImmunology
JF - OncoImmunology
SN - 2162-4011
IS - 4
M1 - e1412901
ER -