Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma

Hepatocellular carcinoma (HCC) has high relapse and low 5-year survival rates. Single-cell profiling in relapsed HCC may aid in the design of effective anticancer therapies, including immunotherapies. We profiled the transcriptomes of similar to 17,000 cells from 18 primary or early-relapse HCC cases. Early-relapse tumors have reduced levels of regulatory T cells, increased dendritic cells (DCs), and increased infiltrated CD8(+) T cells, compared with primary tumors, in two independent cohorts. Remarkably, CD8(+) T cells in recurrent tumors overexpressed KLRB1 (CD161) and displayed an innate-like low cytotoxic state, with low clonal expansion, unlike the classical exhausted state observed in primary HCC. The enrichment of these cells was associated with a worse prognosis. Differential gene expression and interaction analyses revealed potential immune evasion mechanisms in recurrent tumor cells that dampen DC antigen presentation and recruit innate-like CD8(+) T cells. Our comprehensive picture of the HCC ecosystem provides deeper insights into immune evasion mechanisms associated with tumor relapse.

Automated summary

This study showed that early-relapse hepatocellular carcinoma (HCC) tumors exhibit innate-like CD8(+) T cells with overexpression of KLRB1 (CD161) and a low cytotoxic state, unlike the exhausted state seen in primary HCC. These cells were associated with a worse prognosis. Additionally, potential immune evasion mechanisms were identified in recurrent tumor cells, which dampen dendritic cell antigen presentation and recruit innate-like CD8(+) T cells.