Patients' NK cell stimulation with activated plasmacytoid dendritic cells increases dinutuximab-induced neuroblastoma killing.
Cancer Immunol Immunother
; 69(9): 1767-1779, 2020 Sep.
Article
de En
| MEDLINE
| ID: mdl-32342128
ABSTRACT
Targeted immunotherapy has improved the outcome of patients with high-risk neuroblastoma (NB). However, immune escape of tumor cells still occurs and about 40% of NB patients relapse and die from their disease. We previously showed that natural killer (NK) cell stimulation by Toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDC) increases the efficacy of dinutuximab-based immunotherapy against NB cell lines via the TRAIL death-receptor pathway. With the aim to translate our findings into a novel adoptive therapy of TLR-activated pDC, we investigated the pDC/NK cell axis in NB patients undergoing dinutuximab-based immunotherapy. We show that pDC counts were low at the beginning of immunotherapy but reached normal levels over time. Blood NK cell counts were normal in all patients, although a high proportion of CD56bright CD16low/- cells was observed. The stimulation of patient's blood cells with a TLR9 ligand led to IFN-α production by pDC, and TRAIL expression on NK cell surface. Patient's NK cells expressed high levels of CD69 and TRAIL after stimulation with activated pDC. Both CD56bright CD16low/- and CD56dim CD16+ NK cells degranulated against autologous target cells in the presence of dinutuximab. Importantly, pDC-induced NK cell activation increased the dinutuximab mediated autologous killing of patient-derived NB cells. Altogether, our study demonstrates that TLR-activated pDC strongly increase the cytotoxic functions of NK cells in high-risk NB patients undergoing immunotherapy. These results, therefore, support pDC adoptive immunotherapy as a novel approach to decrease the risk of relapse in patients with high-risk NB.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Cellules dendritiques
/
Cellules tueuses naturelles
/
Anticorps monoclonaux
/
Neuroblastome
Limites:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
Langue:
En
Journal:
Cancer Immunol Immunother
Sujet du journal:
ALERGIA E IMUNOLOGIA
/
NEOPLASIAS
/
TERAPEUTICA
Année:
2020
Type de document:
Article
Pays d'affiliation:
Canada