Are myeloid-derived suppressor cells (MDSC) a predictive marker to evaluate pancreatic ductal adenocarcinoma progression?

In several human cancer types and in tumor-bearing mouse models, tumor-derived factors sustain the accumulation and functional differentiation of myeloid cells, including myeloid-derived suppressor cells (MDSCs), which can interfere with T cell-mediated responses. The aim of this study was to characterize MDSCs presence in the circulation of pancreatic ductal adenocarcinoma (PDAC) patients and to evaluate their importance as biomarkers. Our results show that monocytic MDSC (MO-MDSC) are significantly expanded in PDAC patient compared to healthy controls. Within the PDAC donors, a group displays monocytes with immune suppressive ability on T cells and this phenotype is accompanied with a specific gene expression profile different from that of non-suppressive cells both of patients and control origin. Our observations suggest that a specific genetic “barcode” identify suppressive PDAC MO-MDSC and this tool can potentially be used as prognostic factor as well as important additional information regarding the need of an immunological treatment or co-treatment of pancreatic cancer. The dynamic interplay between human cancer and host immune system can be studied in vivo in mice repopulated with human hematopoietic cells (HIR mice). Here we describe an easy tool to sustain human myelopoiesis in these models delivering human cytokines via adeno associated virus (AAV) and we apply it for the study of pancreatic cancer. We show that the presence of the human immune system promotes cancer progression, as lung micrometastasis frequency is significantly increased in tumor-bearing HIR mice compared to controls. Human leukocytes that infiltrate the pre-metastatic niche are characterized by a genetic signature strongly related to the myeloid compartment and to inflammation. Among the upregulated factors, we find protein S100B, whose serum level is also significantly different compared to control and chronic pancreatitis patients. This study opens up new possibilities for the characterization of a genetic "barcode" useful to identify suppressive MO-MDSC in patients with pancreatic adenocarcinoma. This work may also enable the identification of important elements of the immune system that can promote tumor progression.