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

By Yunfan Sun, Liang Wu, Y. Zhong, Kaiqian Zhou, Yong Hou, Zifei Wang, Zefan Zhang, Jiarui Xie, Chunqing Wang, Dandan Chen and 24 more. Cell, 2020

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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 ∼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.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/817682f2c79ec0d8caadbf06741006e9ed7a25a8

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