Combining immune stimulation with inhibition of immune suppression to boost innate immunity in cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a common gastrointestinal malignancy characterized by rapid progression, resulting in poor outcome and a 5-year survival rate of less than 5%. There are no effective therapies for PDAC, except for surgical resection which has a minor impact on survival. In order to improve clinical outcome, new therapeutic strategies are needed.PDAC is characterized by a dense desmoplastic reaction, primarily reflecting the activation of pancreatic stellate cells (PSC). PSC become activated in response to growth factors, oxidative stress and changes in tissue plasticity. Activated PSC within the PDAC stroma have an impact on the migration of immune cells towards malignant lesions, playing an important role in modulation of the crosstalk between neoplastic, stromal and immune cells. In PDAC, the ability of the immune system to identify and eliminate neoplastic cells is compromised, suggesting that an immunosuppressive environment is established. Immunotherapy can potentially be a powerful new component of PDAC treatment. However, in order to obtain immune-mediated elimination of PDAC, most likely immune stimulation must be combined with a strategy that overcomes the immunosuppressive environment.Further study of the mechanisms by which immunosuppression is initiated in PDAC, and ways to overcome it, will facilitate the development of this treatment option. Here, we will focus on unraveling the interactions between PSC, innate immune cells and tumor cells in order to identify new therapeutic targets. Experiments will be performed in vitro and in vivo.

Keywords:INNATE IMMUNITY, ONCOLOGY, IMMUNOTHERAPY

Disciplines:Immunology, Morphological sciences, Oncology