期刊
CELL
卷 184, 期 2, 页码 404-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2020.11.041
关键词
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资金
- China National GeneBank
- State Key Program of National Natural Science of China [81530077, 81830102]
- National Natural Science Foundation of China [81602543, 81672839, 81772578, 81772551, 82073222, 82072715]
- National Key R&D Program of China [2019YFC1315800, 2019YFC1315802]
- Natural Science Foundation of Guangdong Province [2018A030313379]
- Guangdong Provincial Key Laboratory of Genome Read and Write
- Shanghai Municipal Health Commission Collaborative Innovation Cluster Project [2019CXJQ02]
- Shanghai Science and Technology Commission [19QA1402000]
- Guangdong Province Science and Technology Program [2016B030229007]
- Guangdong-Hong Kong Joint Laboratory on Immunological and Genetic Kidney Diseases [019B121205005]
- Science, Technology and Innovation Commission of Shenzhen Municipality [GJHZ20180419190827179]
- Shenzhen Key Laboratory of Single-Cell Omics [ZDSYS20190902093613831]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA12020105, XDA12020103]
- NIH Intramural Program
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.
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.
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