Abstract 2644: Relative T regulatory cell populations are indicative of HCC in patients with underlying liver disease
Authors: Skill Nicholas J. , Maluccio Mary A. 
Published: August 2018

Abstract
Hepatocellular carcinoma continues to be an increasing burden to patients and the health care system despite recent advances in treatment of viral hepatitis. Since the vast majority of cancers develop in patients with underlying liver disease, we would expect that efforts to cull out the patients at highest risk for cancer emergence would be possible, yet we have struggled to do so. The difficulty lies in the complex microenvironment of the diseased liver that leads to striking aberrancies, many of which are related to inflammation and can overlap with biomarkers felt to be related to cancer. Our goal with lymphocyte profiling is to stratify patients with underlying liver disease into those with and without cancer. Improved surveillance modalities for patients at highest risk of developing HCC are required. Moreover, there is an increasing push to include immunology in cancer detection and treatment. To address these issues, we performed lymphocyte profiling in patients with underlying liver disease with and without HCC and living related renal donors (LRD) by selective cell marker staining and flow cytometry, in order to determine if lymphocytes, which are key to cancer immunology, are modulated concordant with HCC. Specifically, whole blood was stained in order to quantitate T helper (Th), T cytotoxic (Tctx), B cells, natural killer (NK), and T regulatory cells (Treg) by flow cytometry. Th, Tctx and B cells were significantly reduced and NK cells were significantly increased in patients with underlying liver disease. These changes were independent of HCC diagnosis. In contrast, Treg cell levels were dependent on HCC diagnosis. In patients with underlying liver disease without HCC, Treg levels, when compared to LRD (30±6cells/mm3), were significantly reduced (15±3), whereas in patients with underlying liver disease and HCC, Treg levels were increased when compared to patients without HCC and unchanged when compared to LRD (28±6). To correct for the observed lower T-cell levels associated with underlying liver disease, lymphocyte populations were expressed as a ratio when compared to total T-cell numbers. This conversion identified proportional Treg cells population as a marker of HCC. In patients without HCC the Treg/T cell ratio was unchanged when compared to living related donors (0.02±0.002, 0.02±0.002, P=0.3). In contrast, Treg/Tcell ratio was significantly increased in patients with HCC (0.08±0.02, P=0.001). Consequently, given that the primary function of Treg cells is to inhibit T cytotoxic cells, a proportional increase in Treg cells would be associated with immunologic escape for HCC cells. Therefore, surveillance of lymphocyte populations, in particular T cells and Treg, would evaluate changes in immunologic capacity and increased Treg/Tcell ratio would be indicative of an increased risk for HCC in patients with underlying liver disease.
Citation Format: Nicholas J. Skill, Mary A. Maluccio. Relative T regulatory cell populations are indicative of HCC in patients with underlying liver disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2644.