TY - JOUR
T1 - TLR3 triggering regulates PD-L1 (CD274) expression in human neuroblastoma cells
AU - Boes, Marianne
AU - Meyer-Wentrup, Friederike
N1 - Publisher Copyright:
© 2015 Elsevier Ireland Ltd.
PY - 2015/5/28
Y1 - 2015/5/28
N2 - Neuroblastoma is the most common extracranial solid tumor in children, causing 12% of all pediatric cancer mortality. Neuroblastoma specific T-cells have been detected in patients, but usually fail to attack and eradicate the tumors. Tumor immune evasion may thus play an important role in neuroblastoma pathogenicity. Recent research in adult cancer patients shows that targeting T-cell check-point molecules PD-1/PD-L1 (or CD279/CD274) may bolster immune reactivity against solid tumors. Also, infections can be associated with spontaneous neuroblastoma regression. In our current study, we therefore investigated if antibody targeting of PD-L1 and triggering of selective pathogen-receptor Toll-like receptors (TLRs) potentiates immunogenicity of neuroblastoma cells. We find this to be the case. TLR3 triggering induced strong upregulation of both MHC class I and PD-L1 on neuroblastoma cells. At the same time TGF-β levels decreased and IL-8 secretion was induced. The combined neuroblastoma cell treatment using PD-L1 blockade and TLR3 triggering using virus analog poly(I:C) moreover induced CD4+ and CD8+ T-cell activation. Thus, we propose combined treatment using PD-L1 blockade with synthetic TLR ligands as an avenue toward new immunotherapy against human neuroblastoma.
AB - Neuroblastoma is the most common extracranial solid tumor in children, causing 12% of all pediatric cancer mortality. Neuroblastoma specific T-cells have been detected in patients, but usually fail to attack and eradicate the tumors. Tumor immune evasion may thus play an important role in neuroblastoma pathogenicity. Recent research in adult cancer patients shows that targeting T-cell check-point molecules PD-1/PD-L1 (or CD279/CD274) may bolster immune reactivity against solid tumors. Also, infections can be associated with spontaneous neuroblastoma regression. In our current study, we therefore investigated if antibody targeting of PD-L1 and triggering of selective pathogen-receptor Toll-like receptors (TLRs) potentiates immunogenicity of neuroblastoma cells. We find this to be the case. TLR3 triggering induced strong upregulation of both MHC class I and PD-L1 on neuroblastoma cells. At the same time TGF-β levels decreased and IL-8 secretion was induced. The combined neuroblastoma cell treatment using PD-L1 blockade and TLR3 triggering using virus analog poly(I:C) moreover induced CD4+ and CD8+ T-cell activation. Thus, we propose combined treatment using PD-L1 blockade with synthetic TLR ligands as an avenue toward new immunotherapy against human neuroblastoma.
KW - Immune checkpoint blockade
KW - Immune therapy
KW - Neuroblastoma
KW - PD-1/PD-L1
KW - Therapeutic antibodies
KW - TLR ligands in cancer therapy
UR - http://www.scopus.com/inward/record.url?scp=84925047708&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2015.02.027
DO - 10.1016/j.canlet.2015.02.027
M3 - Article
C2 - 25697485
AN - SCOPUS:84925047708
SN - 0304-3835
VL - 361
SP - 49
EP - 56
JO - Cancer Letters
JF - Cancer Letters
IS - 1
ER -