Myeloid derived suppressor cells in patients with Pancreatic Adenocarcinoma

Abstract

Background: Pancreatic cancer (PC) often presents late with poor survival. While the role of immune suppressive cells in pre-clinical studies has generated immunotherapeutic agents, these cells remain under investigated in PC. Myeloid derived suppressor cells (MDSC) are heterogeneous immature myeloid cells that negatively regulate the immune responses during tumour progression, inflammation, and infection. Aim: The aim of this study was to characterise the different subsets of MDSCs and evaluate their levels and functions in the circulation and tissue of PC patients. Methods: Flow cytometric staining was performed on peripheral blood samples of 24 PC patients, 12 patients with chronic pancreatitis (CP) and 16 healthy donors. Tumour (n=7) and benign (n=7) pancreatic tissue samples were also examined for comparative analysis. Results: Significant increases in circulating and tumour-infiltrating granulocytic (Lin-HLA-DR-CD33+CD11b+CD15+), but not monocytic (Lin-HLA-DR-CD14+), MDSC were observed in patients with PC when compared with healthy donors and age-matched patients with benign pancreatic disease (CP). The circulating MDSCs from PC patients expressed arginase 1 (ARG 1), which represents their functional state. Blood levels of MDSC showed no association with PC stage or preoperative levels of tumour markers. Conclusions: Our findings provide a first characterisation of the phenotype of different subsets of peripheral and local MDSCs in PC patients and suggest that the frequency and contribution of these cells are predominantly granulocytic. These findings suggest that MDSCs have a role in pancreatic cancer. Future large validation studies may help the development of new immunotherapeutic strategies to inhibit and eliminate MDSCs in PC.

Date of Award	1 Aug 2015
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Basil Ammori (Supervisor) & Eyad Elkord (Supervisor)