Clinical Relevance of Circulating and Splenic Immature Myeloid Cells in Pancreatic Diseases.

Context Blood and spleen expansion of immature myeloid cells might compromise the immune response to cancer, enabling tumor outgrowth and metastasis. Objective To study the pattern of circulating and splenic lymphocyte subsets and immature myeloid cells in patients with benign and malignant pancreatic diseases. Patients and Methods One-hundred and three pancreatic and/or splenic surgical patients were enrolled (52 ductal adenocarcinoma (PaCa), 10 NETs, 10 IPMNs, 9 SCA, 9 non-pancreatic tumors and 13 control cases (chronic pancreatitis, splenic non neoplastic lesions)). In blood and splenic samples, flow cytometric analysis was conducted on lymphoid (CD4+, CD8+, CD4+ CD25+ T cells) and myeloid cells (CD33+ CD14+ HLA-DR+, CD33+ CD14+ HLA-DR-, CD33+ CD14- HLA-DR+ and CD33+ CD14- HLA-DR-). Inhibitory molecules PDL-1 and CTLA4 were also studied in immature myeloid cells in 30 splenic samples. Results In PaCa a significant reduction was found in circulating cytotoxic CD8+ T cells (P=0.015) and CD33+ CD14- HLA-DR+ dendritic cells (P=0.01), whereas in spleen samples these latter cells were increased in patients with both exocrine and endocrine malignant pancreatic tumors (P=0.077). Circulating and splenic CD33+ CD14+ HLA-DR- cells, potentially immunosuppressive, were increased in patients who developed disease recurrence or died after surgery for the disease (P=0.0023). In PaCa, splenic dendritic cells had a higher PDL-1 expression (P=0.028) while CD33+ CD14+ HLA-DR- cells had a lower CTLA4 expression (P=0.029) than in samples from other diseases. Conclusion Among exocrine and endocrine benign or malignant pancreatic tumors, PaCa mainly imbalances immune cells pattern. Reduced circulating dendritic and cytotoxic T cells might favour PaCa growth, while the expansion of CD33+ CD14+ HLA-DR- cells, potentially immunosuppressive, might favour tumor progression. PaCa might affect immune cells by targeting PDL-1 and CTLA4 molecules.