Comprehensive Analyses of the Infiltrating Immune Cell Landscape and Its Clinical Significance in Hepatocellular Carcinoma

BACKGROUND: Immunotherapy has gradually played a significant role in treating cancer over the past 10 years. Meanwhile, significant connections have been found between infiltrating immune cells and prognosis, as well as the development of immunotherapy in hepatocellular carcinoma (HCC). Thus, analyses of the immune cell landscape are urgently needed for the future development of immunotherapy in HCC. METHODS: Expression data of HCC and normal liver tissue were searched and downloaded from The Cancer Genome Atlas. The fraction of various immune cells was estimated by CIBERSORT, which is a computational analysis tool. Comparisons of the fractions of 22 types of immune cells were performed between HCC and normal tissues, as well as survival analyses and clinical significance. xCell was used to validate the results. RESULTS: The fractions of 12 types of immune cells, including follicular helper T (Tfh) cells, monocytes, M0, and M2 macrophages, were significantly different between tissues. In survival analyses, higher fractions of Tfh cells (P=0.037), M0 (P=0.001), and M2 macrophages (P=0.045) were associated with a poorer prognosis, and monocytes with a better prognosis (P=0.040). Furthermore, a higher fraction of M0 macrophages (P=0.001), lower fraction of monocytes (P=0.031), and M2 macrophages (P=0.018) were found as risk factors of a poorer histological grade of HCC. Only M0 macrophages showed a significant association with the clinical stage of HCC. Meanwhile, xCell showed monocytes and M2 macrophages significantly reduced in tumor tissues, which validated the results. CONCLUSION: Tfh cells, monocytes, M0 and M2 macrophages may play an indicator role in carcinogenesis, progression, and clinical outcomes of HCC. Our research can serve as a reference contributing to future immunotherapy strategies of HCC.