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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE277055 | GEO | 2025/06/04

REPOSITORIES: GEO

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Project description:The paper describes a model on the size of pancreatic tumour. Created by COPASI 4.25 (Build 207) This model is described in the article: Modeling Pancreatic Cancer Dynamics with Immunotherapy Xiaochuan Hu, Guoyi Ke and Sophia R.-J. Jang Bulletin of Mathematical Biology (2019) 81:1885–1915 Abstract: We develop a mathematical model of pancreatic cancer that includes pancreatic cancer cells, pancreatic stellate cells, effector cells and tumor-promoting and tumor- suppressing cytokines to investigate the effects of immunotherapies on patient survival. The model is first validated using the survival data of two clinical trials. Local sen- sitivity analysis of the parameters indicates there exists a critical activation rate of pro-tumor cytokines beyond which the cancer can be eradicated if four adoptive trans- fers of immune cells are applied. Optimal control theory is explored as a potential tool for searching the best adoptive cellular immunotherapies. Combined immunother- apies between adoptive ex vivo expanded immune cells and TGF-β inhibition by siRNA treatments are investigated. This study concludes that mono-immunotherapy is unlikely to control the pancreatic cancer and combined immunotherapies between anti-TGF-β and adoptive transfers of immune cells can prolong patient survival. We show through numerical explorations that how these two types of immunotherapies are scheduled is important to survival. Applying TGF-β inhibition first followed by adoptive immune cell transfers can yield better survival outcomes. This model is hosted on BioModels Database and identified by: MODEL1907050003. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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

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