Antibody-mediated blockade of the immune-inhibitory PD-1–PD-L1 signaling pathway prolongs survival in poly(I:C)-treated mice. Antibody-mediated blockade.

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Antibody-mediated blockade of the immune-inhibitory PD-1–PD-L1 signaling pathway prolongs survival in poly(I:C)-treated mice. Antibody-mediated blockade of the immune-inhibitory PD-1–PD-L1 signaling pathway prolongs survival in poly(I:C)-treated mice. A, upregulation of MHC class I (MHCI) and PD-L1 on the surface of HCmel3 melanoma cells following exposure to IFNα or IFNγ in vitro. B, correlation of relative mRNA expression levels for PD-L1 and IRF7 in untreated and poly(I:C)-treated HCmel3 melanoma samples determined by quantitative reverse transcriptase PCR (qRT-PCR). C, representative histograms showing the percentage of PD-1–expressing CD8+ T cells (left) and cumulative data for a correlation of PD-1 expression on CD8+ T cells in the blood of HCmel3-bearing mice treated as indicated (right). D, experimental protocol for combination therapy for transplanted HCmel3 melanomas with poly(I:C) and anti–PD-1 antibody. E, representative tumor growth kinetics of HCmel3 melanomas in individual mice treated as indicated (n = 5). Similar results were obtained in at least two independent treatment cohorts. F, corresponding Kaplan–Meier survival curves (left) and mean survival of mice treated as indicated (right); mean ± SEM; n = 10; *, P < 0.05; n.s., nonsignificant; IgG, immunoglobulin G; i.c., intracutaneous. Tobias Bald et al. Cancer Discovery 2014;4:674-687 ©2014 by American Association for Cancer Research