Myeloid derived suppressor cells are reduced and T regulatory cells stabilised in patients with advanced pancreatic cancer treated with gemcitabine and intravenous omega 3.
Pancreatic cancer
T regulatory cells (Tregs)
myeloid derived suppressor cells (MDSCs)
omega 3 fatty acids (ω-3FAs)
Journal
Annals of translational medicine
ISSN: 2305-5839
Titre abrégé: Ann Transl Med
Pays: China
ID NLM: 101617978
Informations de publication
Date de publication:
Mar 2020
Mar 2020
Historique:
entrez:
21
4
2020
pubmed:
21
4
2020
medline:
21
4
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 32309319
doi: 10.21037/atm.2020.02.02
pii: atm-08-05-172
pmc: PMC7154395
doi:
Types de publication
Journal Article
Langues
eng
Pagination
172Informations de copyright
2020 Annals of Translational Medicine. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest: The authors have no conflicts of interest to declare.
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