Effect of depletion of PARP2 on gene expression in 3 month-old pancreas from Ela-myc mice

Pancreatic cancer represents one of the most lethal tumours, characterised by an immunosuppressive microenvironment and a lack of cytotoxic immune cell infiltrates, which confers resistance to immunotherapy. Here, we demonstrate that the deletion of Poly(ADP-ribose)polymerase 2 (PARP2) delays tumour progression in c-Myc-driven and KRas-driven mouse models of pancreatic cancer. Transcriptomic analysis revealed that the absence of PARP2 induces an enrichment of pathways associated with anti-tumor immune responses and genomic instability. Analysis of tumour-infiltrating immune cells within the tumor microenvironment showed that PARP2 deletion leads to an increase in effector CD4 and CD8 T cells as well as natural killer (NK) cells, accompanied by a significant reduction in pro-tumor regulatory T (Treg) cells and M2 macrophages. Collectively, our data support that selective PARP2 inhibition is a promising therapeutic strategy for pancreatic cancer by boosting anti-tumor immune response, thereby opening new avenues for combating this recalcitrant neoplasia. Overall design: To investigate the role of PARP2 in pancreatic tumor development, we isolated pancreatic tissue from 3-month old Ela-myc wildy type and PARP2 knocked-out animals. We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different animals of each genotype (WT or PARP2 KO).