Pro-Inflammatory Serum Marker Profiles That Lack Upregulated Il-17 Are Characteristic For Pancreatic Cancer And Require For Further Anti-Tumor Immune Response And Strategies.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest types of cancer with 5-year survival rates between 5-8%. Chronic inflammation of the pancreas and pancreatitis is thought to be a risk factor in PDAC. The aim of this study was to elucidate characteristic pro-inflammatory cytokines and chemokines including IL-17 profiles in human pancreatic cancer. A total of 186 individuals with confirmed PDAC (n=116), chronic pancreatitis (n=32), and healthy volunteers (n=38) were included in the study. The histological stage of the tumor was determined according to the Union for International Cancer Control (UICC) TNM staging system. Tumors were evaluated for stage and differentiation grade. Data concerning age, gender, level of wall infiltration, lymph node metastasis, and distant metastases were collected in a database. Additional clinical characteristics necessary for statistical analysis of the data from the study population were collected from the Tumor Registry. Inflammation-related cytokines and chemokines in IL-17 pathway among the patients were analyzed from serum obtained pre-operatively and compared with healthy controls. Moreover, the KEGG PATHWAY, a collection of manually drawn pathway maps on molecular interaction, reaction and relation networks was used for IL-17 pathway analysis. Non-parametric tests and correlation tests were utilized to compare the factors among three groups for statistical analysis. Pancreatitis patients showed highest expression in inflammatory cytokines and chemokine panels while those with PDAC showed different profiles. Pro-inflammatory cytokines including IL-5, IL-6, CXCL8, CCL2, TNF-alpha, and IFN-gamma revealed higher expression in PDAC patients than healthy volunteers (P<0.05). Anti-inflammatory cytokines like IL-13 demonstrated lower expression in PDAC patients than healthy controls (P<0.05), which was likewise observed for IL-17. Interestingly, PDAC patients with distant metastases showed lower pro-inflammatory expression profiles than those with localized tumors. Moreover, correlation analysis demonstrated that IL-17 was correlated with IL-13 and GM-CSF expression (P<0.05). In conclusion, we provide evidence that PDAC patients are characterized by dominant expression of pro-inflammatory cytokine profiles, diminished IL-17 level within their serum, and also anti-inflammatory mediators within is in part divergent from other solid cancers. The IL-17 signaling. may therefore play a different role in the inflammatory pathway in pancreatic cancer. Citation Format: Yueming Luo, Martin Gasser, Amrendra Ajay, Li-LI Hsiao, Ana Maria Waaga-Gasser. Pro-inflammatory serum marker profiles that lack upregulated IL-17 are characteristic for pancreatic cancer and require for further anti-tumor immune response and strategies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1758.