PD-L1 blockade improves response of pancreatic adenocarcinoma to radiotherapy

Abul Azad1,Zenobia D’Costa1,Owen Sansom2,W.Gillies McKenna1,Ruth Muschel1,Emmanouil Fokas1

1Cancer Research UK/MRC Oxford Institute for Radiation Oncology, Oxford, UK,2Cancer Research UK Beatson Institute, Glasgow, Institute of Cancer Sciences, University of Glasgow, Glasgow, Glasgow, UK

Presenting date: Monday 2 November
Presenting time: 16.10-16.25


The programmed death ligand 1 (PD-L1) plays a key role in tumour progression and metastasis of pancreatic ductal adenocarcinoma (PDAC). Although recent preclinical studies have explored the radiosensitising potential of PD-1/PD-L1 inhibitors, the effect of PD-L1 blockade on the response of PDAC to radiotherapy remains unexplored.


Herein, we investigated the influence of an anti-PD-L1 mAb on the tumour response to single dose and fractionated radiotherapy, and chemotherapy with gemcitabine and capecitabine.


In-vitro, radiation and chemotherapy resulted in PD-L1 upregulation in both human (PSN-1) and murine (KPC-derived, Pan02) PDAC cells, although variability was observed. Exposure to conditioned media from pre-treated cells did not alter PD-L1 expression. In-vivo, PD-L1 was also upregulated in the tumour microenvironment after radiation and chemotherapy in the KPC-derived and Pan02 syngeneic mouse models. Similarly, chemotherapy induced PD-L1 upregulation in the KPC (Pdx1Cre, KRASG12D/+, P53R172H/+), a genetically-engineered mouse model of pancreatic cancer. In-vitro, PD-L1 blockade failed to radio- or chemosensitise PDAC cells. The anti-PD-L1 mAb significantly improved tumour response after irradiation in the KPC and Pan02 syngeneic mouse models. This effect was mediated by a cytotoxic T cell-dependent mechanism, whereas blockade of CD8+ cells attenuated the radiosensitising potential of anti-PD-L1. The effect of scheduling of anti-PD-L1 mAb with radiotherapy (concomitant vs sequential) was also investigated. Finally, we assessed the intratumoural and systemic expression of several immune markers (CD45+: CD8, CD4, CD19, NK1.1, CD11b Gr1, Ly6G, CXCR2, FOXP3, IFN-?) after the different treatments.



Altogether, our findings support PD-L1 inhibition in combination with radiation as a promising approach in the treatment of PDAC.