Myeloid derived suppressor cells are reduced and T regulatory cells stabilised in patients with advanced pancreatic cancer treated with gemcitabine and intravenous omega 3

John Isherwood; Ali Arshad; Wen Yuan Chung; Franscois Runau; Jill Cooke; Cristina Pollard; Lynne Howells; Jenny Fishwick; John Thompson; Matthew Metcalfe; William Steward; Ashley Dennison

doi:10.21037/atm.2020.02.02

Myeloid derived suppressor cells are reduced and T regulatory cells stabilised in patients with advanced pancreatic cancer treated with gemcitabine and intravenous omega 3

Ann Transl Med. 2020 Mar;8(5):172. doi: 10.21037/atm.2020.02.02.

Affiliations

¹ Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, Leicester, UK.
² Leicester Cancer Research Centre, Leicester Royal Infirmary, Leicester, UK.
³ Department of Health Sciences, University of Leicester, Leicester, UK.

Abstract

Background: Pancreatic adenocarcinoma (PAC) is a devastating condition, with the majority of patients presenting with metastatic or locally advanced disease. In these patients their disease is classified as advanced pancreatic cancer (APC), which is incurable and associated with survivals generally of a few months. The overall survival (OS) for pancreatic cancer has not changed significantly in the past forty years with multiple trials demonstrating disappointing results. Immune modulatory cells particularly myeloid derived suppressor cells (MDSCs) and T regulatory cells (Tregs) are important mediators in PAC. Omega 3 fatty acids (ω-3FAs) have been shown to have anti-inflammatory properties and there is now evidence demonstrating the benefit of ω-3FAs in PAC.

Methods: This was a single-center cohort study investigating intravenous ω-3FAs and gemcitabine chemotherapy versus gemcitabine therapy only in patients with APC. Here, we investigated levels of MDSCs and Tregs and examined how these changes correlated with survival.

Results: Eighteen trial and nine control patients were recruited. There was a significant benefit in progression-free survival (PFS) in trial compared to control patients (P=0.0003). Median survival in trial patients was 5.65 months compared to 1.8 months in control patients. There was no significant benefit in OS in trial compared to control patients (P=0.13). Median survival in trial patients was 7 months compared to 2.9 months in control patients. MDSCs were significantly decreased in trial patients (P=0.0001) but not control patients. Conversely Tregs were significantly increased in control patients (P=0.005) but not in trial patients.

Conclusions: Administration of ω-3FAs with gemcitabine chemotherapy in APC results in a significant decrease of MDSCs and stability of Tregs. This may be secondary to the reduction of pro-inflammatory mediators. A phase three randomized trial is justified to further examine these effects.

Keywords: Pancreatic cancer; T regulatory cells (Tregs); myeloid derived suppressor cells (MDSCs); omega 3 fatty acids (ω-3FAs).