IL-6 and PD-L1 antibody blockade combination therapy reduces tumour progression in murine models of pancreatic cancer

Objective Limited efficacy of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) has prompted investigation into combination therapy. We hypothesised that interleukin 6 (IL-6) blockade would modulate immunological features of PDAC and enhance the efficacy of anti-programmed death-1-ligand 1 (PD-L1) checkpoint inhibitor therapy. Design Transcription profiles and IL-6 secretion from primary patient-derived pancreatic stellate cells (PSCs) were analyzed via Nanostring and immunohistochemistry, respectively. In vivo efficacy and mechanistic studies were conducted with antibodies (Abs) targeting IL-6, PD-L1, CD4 or CD8 in subcutaneous or orthotopic models using Panc02, MT5 or KPC-luc cell…

• AC
  American-Italian Cancer Foundation
• LF
  Lustgarten Foundation
• P
  Pelotonia
• NI
  National Institutes of Health

  Awards: P30CA016058, KL2TR001068, CA016058, UL1RR025755, 5T32CA009338, P30 CA016058
• NO
  NIH Office of the Director

  Award: P30 CA016058
• NC
  National Cancer Institute

  Awards: P30CA016058, 5T32CA009338, UL1RR025755, CA016058, P30 CA016058, 1R01CA208253-01
• NC
  National Center for Research Resources

  Award: UL1RR025755
• NC
  National Center for Advancing Translational Sciences

  Awards: UL1RR025755, KL2TR001068