Reprogramming tumour-associated macrophages with proton irradiation to boost the effects of immunotherapy in pancreatic cancer

Project: ResearchResearch, Dissertation project

Description

Pancreatic ductal adenocarcinoma (PDAC), the most frequent type of
pancreatic cancer, represents one of the deadliest malignancies with a
median survival of less than 12 months. Therefore, there is an urgent need
for the development of new treatment modalities. For this reason, the
rewiring of the tumour microenvironment to induce anti-tumour immunity is
currently under investigation. Tumour-associated macrophages (TAMs)
represent the most abundant immune cells in the tumour and more than
70% of them are M2-like macrophages with immunosuppressive activities.
The reprogramming of TAMs to M1 phenotype would thus be a key for
effective immunotherapy. It has been demonstrated that conventional
radiotherapy is unable to reprogram TAMs towards a M1 phenotype.
Preliminary results generated by our research group showed that proton
irradiation modified the phenotype of human M2 macrophages in vitro. The
aim of this proposal is to compare both types of irradiation using appropriate
in vitro cell cultures and an in vivo murine tumour model to study the
reprogramming of macrophages, the mechanisms implicated in the
reprogramming of macrophages as well as the dialogue between cancer
cells and macrophages in order to delineate new therapeutic modalities for
pancreatic cancer.
Short titlePROTON-TAMs
StatusActive
Effective start/end date1/10/1830/09/19