Abstract
BackgroundChronic inflammation is involved in the initiation and progression of various cancers, including liver cancer. The current study focuses on the characterization of the peripheral immune response in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) patients, before and after surgical procedure, in order to assess the effect of tumor resection in the immune system homeostasis and to determine possible prognostic factors associated with high-grade tumors. We developed a whole-blood assay to monitor immune alterations and functional competence of peripheral monocytes in a group of 10 healthy individuals (HG), in 20 HCC patients and 8 CCA patients, by multi-color flow cytometry, qRT-PCR, and ELISA techniques.ResultsThe qRT-PCR analysis showed an upregulation of TNFα expression by classical and intermediate monocytes purified from HCC patients presenting tumors in grade G3-G4 as compared to G1-G2 HCC patients. Moreover, ELISA assay confirmed elevated serum levels of TNFα in G3-G4 compared to G1-G2 HCC patients. A significant decrease of circulating non-classical monocytes was detected in both CCA and HCC patients before and after surgical procedure. In addition, a functional defect in circulating classical and intermediate monocytes was observed in both groups of cancer patients when compared to the HG, with partial recovery after the surgical intervention.ConclusionsThis integrated analysis permitted the identification of altered functional competence of monocyte subsets in CCA and HCC patients. In addition, our results point to a potential role of TNFα as a prognostic peripheral biomarker in HCC patients, indicating the presence of high-grade tumors that should be further validated.
Highlights
Chronic inflammation is involved in the initiation and progression of various cancers, including liver cancer
CCA patients displayed a significant decrease in the absolute numbers of peripheral blood (PB) classical, intermediate and non-classical monocytes, both at T0 and T1, when compared to the HG, and a significant decrease in the relative frequency of non-classical monocytes at T0 in comparison to the HG, that was partially restored at T1
The detected increase in the circulating levels of CCL20, CXCL10, and TNFα suggests a peripheral proinflammatory state in hepatocellular carcinoma (HCC) and CCA patients and an activate state for monocyte subsets classical and intermediate monocyte subsets displayed a functional defect at T0 and, a limited capacity to respond under further stimulation processes. This integrated analysis permitted the identification of different immune background in CCA and HCC patients, as well as altered functional competence of circulating monocytes in these carcinomas
Summary
Chronic inflammation is involved in the initiation and progression of various cancers, including liver cancer. Liver cancer is the second most common cause of cancer-related death worldwide, with a steady increasing incidence and mortality [1] and, a major public health challenge. It is considered an immunogenic cancer because 90% of cases develop under conditions of chronic inflammation [1, 2]. Hepatocellular carcinoma (HCC) is the most frequent liver cancer and is associated to high morbidity and mortality rates [1, 4]. It presents poor prognosis, generally due to its late presentation and late diagnostic. A high postoperative tumor recurrence rate significantly decreases long-term survival outcomes [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
