Intratumoural leukocyte infiltration is a prognostic indicator among pancreatic cancer patients with type 2 diabetes

Abstract

BackgroundThe life expectancy of pancreatic cancer patients remains minimal. The disease progression may be influenced by type 2 diabetes (T2D) and inflammatory status, although important gaps persist around their joint effects on disease outcome. The aim of this study was to investigate the clinical significance of the tumour immune microenvironment on pancreatic cancer prognosis in relation to T2D status. MethodTumour-infiltrating macrophages, neutrophils and eosinophils were studied in primary pancreatic tumours and paired lymph node metastases in relation to patient and tumour characteristics, T2D status and overall survival in a retrospective cohort of patients with resectable pancreatic cancer in Sweden. ResultsOf the 80 included pancreatic cancer patients, 22 (27.2%) had T2D. The diabetic pancreatic cancer patients had significantly higher systemic high white blood cell count than those without diabetes (P = 0.028). Macrophage infiltration levels were higher in lymph node metastases compared with primary tumours (P = 0.040) among pancreatic cancer patients with diabetes. Type 2 diabetes or intra-tumoural leukocyte (macrophage, neutrophil or eosinophil) infiltration alone did not significantly influence pancreatic cancer prognosis. However, among cancer patients with T2D high macrophage or neutrophil tumour-infiltration was associated with a significant reduction in overall survival (adjusted hazard ratio [HR] 7.2; 95% CI 1.5–35.0 and HR 5.4; 95% CI 1.1–26.3, respectively). ConclusionThese results demonstrate associations between T2D and enhanced inflammatory processes with significant implications on survival among pancreatic cancer patients with T2D. Validation in larger independent patient cohorts may identify additional prognostic tools and improved treatment strategies for specific patient subsets.