Elaborating the Tumor Ecosystem of Primary and Relapsed Hepatocellular Carcinoma by Single-Cell RNA Sequencing

Abstract

Hepatocellular carcinoma (HCC) has a high relapse rate and low 5-year survival rate. We generated > 20,000 full-length single-cell transcriptomes from 19 primary or relapsed HCC patients, determining unique features of the tumor microenvironment in relapsed as compared to primary HCC. Relapsed tumors have reduced regulatory T cells, and increased dendritic cells (DCs) and infiltrated CD8⁺ T cells. CD8⁺ T cells from relapsed tumors show group 2 innate lymphoid cell like state, with high naïve, low cytotoxic and exhausted signals. The abundance of distinct DC subtypes is associated with good prognosis in primary or relapsed HCC, while FCN1⁺ monocytes are associated with poor prognosis only in relapsed HCC. Differentially expressed genes and interactions analyses reveal potential mechanisms driving immune evasion and tumor survival in relapsed and primary HCC. Together these results provide a compressive understanding of the ecosystem in primary and relapsed tumors, guiding future immune therapy strategies in HCC.

Keywords: single-cell sequencing, tumor ecosystem, immune environment, hepatocellular carcinoma, relapsed tumor, immune therapy, transcriptome