Oncotarget

Priority Research Papers:

NOD mice, susceptible to pancreatic autoimmunity, demonstrate delayed growth of pancreatic cancer

James Dooley, Emanuela Pasciuto, Vasiliki Lagou, Yulia Lampi, Tom Dresselaers, Uwe Himmelreich and Adrian Liston _

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Oncotarget. 2017; 8:80167-80174. https://doi.org/10.18632/oncotarget.21261

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Abstract

James Dooley1,2, Emanuela Pasciuto1,2, Vasiliki Lagou1,2, Yulia Lampi1,2, Tom Dresselaers3, Uwe Himmelreich3 and Adrian Liston1,2

1 Translational Immunology Laboratory, VIB, Leuven, Belgium

2 Department of Microbiology and Immunology, KU Leuven - University of Leuven, Leuven, Belgium

3 Department of Imaging and Pathology, KU Leuven - University of Leuven, Biomedical MRI/MoSAIC, Leuven, Belgium

Correspondence to:

Adrian Liston, email:

Keywords: pancreatic cancer, MRI, immune, NOD

Received: March 08, 2017 Accepted: August 26, 2017 Published: September 24, 2017

Abstract

Pancreatic cancer is a high mortality form of cancer, with a median survival only six months. There are multiple associated risk factors associated, most importantly type 2 diabetes, obesity, pancreatitis and smoking. The relative rarity of the disease, however, has made it difficult to dissect causative risk factors, especially with related risk factors. A major unanswered question with important therapeutic implications is the effect of immunological responses on pancreatic cancer formation, with data from other cancers suggesting the potential for local immunological responses to either increase cancer development or increase cancer elimination. Due to the rarity and late diagnosis of pancreatic cancer direct epidemiological evidence is lacking, thus necessitating a reliance on animal models. Here we investigated the relationship between pancreatic autoimmunity and cancer by backcrossing the well characterised Ela1-Tag transgenic model of pancreatic cancer onto the pancreatic autoimmune susceptible NOD mouse strain. Through longitudinal magnetic resonance imaging we found that the NOD genetic background delayed the onset of pancreatic tumours and substantially slowed the growth rate of tumours after development. These results suggest that elevated autoimmune surveillance of the pancreas limits tumour formation and growth, identifying pancreatic cancer as a promising target for immune checkpoint blockade therapies that unleash latent autoimmunity.


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