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Pancreatic ductal adenocarcinoma exhibits strong metastatic disease at early stages
of primary tumour formation. Despite resection of the primary tumour the prognosis
for patients is dismal. 80% of the patients develop local recurrence.
Therefore, we analysed immune checkpoint blockade using therapeutic PD1-antibody in
a neoadjuvant approach.
We generated a transgenic mouse model for formation of a single resectable primary
tumour at pancreatic tail with distant metastases. This autochthonous growing tumour
was induced by local in situ electroporation of the pancreas with the sleeping beauty
transposon system for genetic modification and transformation of pancreatic cells.
Blockade of the inhibitory receptor PD1 resulted in activation and expansion of tissue
resident antitumoural CD8+ CD103+ T cells within the pancreas. This T cells were accumulated
only at the site of the primary tumour and could not act systemically. The investigation
of the neoadjuvant approach indeed revealed prevention of local tumour recurrence
after resection of the primary tumour. Thereby, distant metastases were not affected.
Further findings displayed that distant metastases could be targeted by NK cells,
while primary tumour of the pancreas was targeted by CD 8 cells.
In conclusion, we could identify tissue resident antitumoural CD8 T cells after PD1
therapy. Surgical intervention using our transgenic mouse model resulted in prevention
of local tumour recurrence after resection of the primary tumour.
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