Abstract 1305: A comprehensive investigation of immune infiltrates in hepatocellular carcinoma

Abstract

Abstract Hepatocellular carcinoma (HCC), a major form of primary liver cancer, is one of the leading causes of cancer-related death, and is caused by a myriad of risk factors from chronic inflammation by viral infection to genetic defects. Recent investigations shed light on the importance and role of immune cells in tumor microenvironment; however, since a majority of studies have focused only on tumor sites, the role of immune cells in tumor-surrounding (or precancerous) area with chronic inflammation was not investigated in HCC in detail. For the treatment of HCC patients, liver transplant (total hepatectomy) has been reported to offer much longer survival and better outcome compared to patients who had local tumor resection (partial hepatectomy). Nonetheless, the significance of tumor-infiltrating immune cells (TICs) established in patients who had suffered from chronic inflammation is still vague. Here, we collected total 122 Korean HCC samples, followed by high-throughput RNA sequencing (RNA-seq), from various premalignant stages—fibrosis and dysplastic nodules, tumors to noncacerous normal liver tissues—enhanced with public RNA-seq datasets including HCC from TCGA. Decomposing immune cell types using the RNA-seq data revealed that TICs are dynamically changed with showing no or weak correlations in the normal liver tissues, while being intertwined into dense and strong correlation networks as the disease progresses. Intriguingly, patients who had total hepatectomy showed different composition of immune cells and longer disease-free survival compared to the partial hepatectomy group; however, the presence of regulatory T cells (Tregs) before the transplantation dampened this outcome in the total hepatectomy patients. Tregs in the total hepatectomy group were found to be specific to tumor sites, and were enriched upon tumor progression, while pretreatment, such as embolization, increased the presence of Tregs. Besides the specific immune cells in tumor sites, the composition of certain types of immune cells in tumor-surrounding inflamed tissues was also important for predicting patients' outcomes in HCC. Particularly, alternatively activated macrophages (M2-type) have more predictive power in the patients' outcome when they were inferred from the tumor-surrounding inflamed samples. Our study not only provides a dynamic map of tumor-surrounding and -infiltrating immune cells, but also offers understanding about immune cell networks in the progression of HCC. Citation Format: Sangho Yoon. A comprehensive investigation of immune infiltrates in hepatocellular carcinoma [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 1305.