ITOC2 – 007. Two immune faces of pancreatic adenocarcinoma: Impact of immunosuppression

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human neoplasms, having extremely poor prognosis with a five-year survival rate of <1% and a median survival of 6 months. In contrast to other malignancies, pancreatic cancer is highly resistant to chemotherapy and targeted therapy. Therefore, new treatment options are urgently needed to improve the survival of patients with PDAC. Based on our data showing that patients with higher CD8+ T cell tumour infiltration exhibited prolonged overall and disease-free survival compared to patients with lower or without CD8+ T cell tumour infiltration, we suggested that immunotherapy could be a promising treatment option for PDAC. However, clinical data from the CapRi trial (chemoradioimmunotherapy with interferon-α (IFN)) did not point to an improved efficiency of chemoradiation combined with IFN as compared to chemoradiotherapy alone, suggesting an important role of the immune suppression induced by PDAC and/or unspecific immune stimulation. In support of this hypothesis, we found that the PDAC patients and experimental mice had an increased number of regulatory T cells (Treg), myeloid-derived suppressor cells (MDSC) and overexpression of immunosuppressive molecules B7H1 and CD73. These results allowed us to conclude that PDAC provokes not only an anti-tumour immune response, but also strong immune suppression.