75P - Immune-mediated cystatin A expression in patients with pancreatic ductal adenocarcinoma (75P)

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Personalised Medicine
Presenter Takuya Komura
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors T. Komura1, Y. Sakai1, H. Takabatake1, K. Harada2, T. Ohta3, H. Kitagawa3, S. Kaneko1
  • 1System Biology, Graduate School Of Advanced Preventive Medical Sciences, Kanazawa University, 920-8641 - Kanazawa/JP
  • 2Department Of Human Pathology Kanazawa University, Graduate School Of Medical Science, Kanazawa University, 920-8641 - Kanazawa/JP
  • 3Department Of Gastroenterologic Surgery, Kanazawa University Hospital, 920-8641 - Kanazawa/JP

Abstract

Background

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal malignancy with an extremely poor prognosis due to the lack of an efficient diagnostic tool and any radical treatments, except surgical removal. Therefore, it is extremely important to understand its pathology including the host inflammatory immune response of PDAC for development of novel diagnostic tool as well as treatment alternative. In this study, we investigated the pathological feature of PDAC in the context of CSTA, a cytein protease inhibitor, excamining the blood and PDAC tissues.

Methods

We assessed transcriptional expression of CSTA in peripheral blood cells of 41 patients with PDAC and 20 healthy volunteers by quantitative real-time PCR. Next, serum CSTA concentrations in 36 patients with PDAC and those in 37 healthy volunteers were measured, and its correlation with PDAC clinical parameters was analysed. Furthermore, we measured cytokine profiles of sera from 6 PDAC patients with elevated CSTA concentration in sera and 9 PDAC patients without elevation. We also examined the expression of CSTA, its substrate, cathepsin B, and cytokines, in tumor tissues in 20 surgically resected PDAC tissues by immunohistochemical staining.

Results

We observed increment of CSTA mRNA expression in CD4+ cells of peripheral blood of 41 patients with PDAC compared with that in 20 healthy volunteers. Correspondingly, serum CSTA concentrations in 36 patients with PDAC were higher than those in 37 healthy volunteers, and this increase was correlated with PDAC clinical stage. We found that IFN-g, TNF-a, and IL-1b concentrations in sera were significantly correlated with those of CSTA in sera of PDAC patients. As for tumor tissue analysis, CSTA expression was detected in some tumor tissues and many tumor-infiltrating immune cells, particularly neutrophils. Cathepsin B expression was observed in most tumor tissues and tumor-infiltrating immune cells, particularly macrophages.

Conclusions

CSTA expression was involved in the PDAC inflammatory condition in local tumor microenvironment. The CSTA concentration in peripheral blood of PDAC patients have a possibility of potential role as a PDAC immunopathological biomarker.

Clinical trial identification

Legal entity responsible for the study

Kanazawa University Ethics Committee

Funding

None

Disclosure

All authors have declared no conflicts of interest.