Preclinical study on the effects on the immune system of the ablative techniques (Irreversible Electroporation and Radiofrequency Ablation) in pancreatic cancer"

Starting date
January 1, 2017
Duration (months)
24
Departments
Medicine
Managers or local contacts
Bassi Claudio

Inglese
Pancreatic cancer is the 4th leading cause of cancer death. Irreversible Electroporation (IRE) and
Radiofrequency Ablation (RFA) are novel ablative techniques. Nowadays, they are applied on the locally
advanced form of pancreatic tumor, actually the most frequent diagnosis of the disease. RFA and IRE
induce cellular death in different ways: RFA cause thermal necrosis, IRE induces apoptotis on neoplastic
cells. There are not published studies reporting the effects of these 2 techniques on the immune system of
patients suffering from pancreatic cancer. These presumed immunostimulating effects could be able to
justify the encouraging oncological results obtained with application RFA and IRE on human pancreatic
cancer. The research project presented is based on the application of RFA and IRE on a murine model of
pancreatic cancer, the KPC mouse model, obtained through the hybridization of KrasLSL.G12D/+;
p53R172H/+; PdxCretg/+ genes (KPC mouse model). It does present almost the same genetic mutations of
the human pancreatic cancer; hence it represents a very valid pre-clinical model of pancreatic cancer. In
addition, the immune system of these mice is totally competent. In the first part of the project tumor cell
lines derived from the KPC mouse will be used. They will be injected subcutaneously and/or orthotopically.
After this, RFA and IRE will be applied on KPC transgenic mice models properly selected. After that, the
immune system of these mice will be studied in detail. The results obtained will be interpreted in light of
the fact that we suppose that both RFA and IRE are able to stimulate an anti-tumoral adaptive immune
response, through the release into the circulation of tumoral antigens coming from the cellular death
induced by the ablation.

Project participants

Claudio Bassi
Full Professor