RNA-seq of two Pancreatic ductal adenocarcinoma (PDAC) cell lines BxPC-3 and PANC-1 treated with 3x8 Gy X-rays without or with the PARP7 inhibitors RBN-2397 and KMR-206
Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and is associated with a dismal prognosis. Due to late diagnosis, the disease is frequently locally advanced and not amenable to surgical resection, and only a small fraction of patients benefit from radio- or chemotherapy. Immunotherapy has shown limited efficacy as monotherapy, largely due to the profoundly immunosuppressive tumor microenvironment. Recent studies have demonstrated that anti-tumor immune responses can be elicited in pancreatic cancer through activation of the cGAS-STING and RIG-I-MAVS pathways, particularly in the context of radiation therapy. Notably, a hypofractionated radiation regimen of 3×8 Gy has been shown to be more effective than a single dose in inducing immunogenic cell death, type I interferon (IFN-I) signaling, and pro-inflammatory cytokine production. PARP7 inhibitors have also been reported to promote anti-tumor immunity by activating IFN-I responses in lung and colon cancer. Here, we show that in PDAC cells, PARP7 inhibition potentiates the effects of radiation by enhancing STING- and NF-?B dependent immunogenic signaling, inflammatory gene expression, pro-inflammatory cytokine release, immunogenic cell death, and immune cell activation. We performed RNA-seq analysis of all two PDAC cell lines treated with 3x8 Gy alone, or in combination with two different PARP7 inhibitors RBN-2397 and KMR-206.
Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and is associated with a dismal prognosis. Due to late diagnosis, the disease is frequently locally advanced and not amenable to surgical resection, and only a small fraction of patients benefit from radio- or chemotherapy. Immunotherapy has shown limited efficacy as monotherapy, largely due to the profoundly immunosuppressive tumor microenvironment. Recent studies have demonstrated that anti-tumor immune responses can be elicited in pancreatic cancer through activation of the cGAS-STING and RIG-I-MAVS pathways, particularly in the context of radiation therapy. Notably, a hypofractionated radiation regimen of 3×8 Gy has been shown to be more effective than a single dose in inducing immunogenic cell death, type I interferon (IFN-I) signaling, and pro-inflammatory cytokine production. PARP7 inhibitors have also been reported to promote anti-tumor immunity by activating IFN-I responses in lung and colon cancer. Here, we show that in PDAC cells, PARP7 inhibition potentiates the effects of radiation by enhancing STING- and NF-?B dependent immunogenic signaling, inflammatory gene expression, pro-inflammatory cytokine release, immunogenic cell death, and immune cell activation. We performed RNA-seq analysis of all two PDAC cell lines treated with 3x8 Gy alone, or in combination with two different PARP7 inhibitors RBN-2397 and KMR-206.
European Bioinformatics Institute