期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-020-20171-7
关键词
-
资金
- National Medical Research Council (NMRC), Singapore [NMRC/TCR/015-NCC/2016, NMRC/CIRG/1460/2016, NMRC/CSA-SI/0013/2017, NMRC/CSA-SI/0018/2017, NMRC/OFLCG/003/2018, NMRC/STaR/020/2013, NMRC/CG/M003/2017, LCG17MAY004, NMRC/OFIRG/0064/2017]
- National Research Foundation, Singapore [NRF-NRFF2015-04]
The study reveals significant immune intratumoural heterogeneity in hepatocellular carcinomas, which is closely associated with tumor evolution and poor clinical outcomes. Tumors with high immune heterogeneity demonstrate an immune suppressive microenvironment, indicating a complex interplay between tumor and immune system during disease progression.
The clinical relevance of immune landscape intratumoural heterogeneity (immune-ITH) and its role in tumour evolution remain largely unexplored. Here, we uncover significant spatial and phenotypic immune-ITH from multiple tumour sectors and decipher its relationship with tumour evolution and disease progression in hepatocellular carcinomas (HCC). Immune-ITH is associated with tumour transcriptomic-ITH, mutational burden and distinct immune microenvironments. Tumours with low immune-ITH experience higher immunoselective pressure and escape via loss of heterozygosity in human leukocyte antigens and immunoediting. Instead, the tumours with high immune-ITH evolve to a more immunosuppressive/exhausted microenvironment. This gradient of immune pressure along with immune-ITH represents a hallmark of tumour evolution, which is closely linked to the transcriptome-immune networks contributing to disease progression and immune inactivation. Remarkably, high immune-ITH and its transcriptomic signature are predictive for worse clinical outcome in HCC patients. This in-depth investigation of ITH provides evidence on tumour-immune co-evolution along HCC progression. Intratumoural heterogeneity is a feature of liver cancer. Here, the authors demonstrate that heterogeneity exists at the immune cell level in liver cancer and show that tumours with high intratumoural immune heterogeneity demonstrated an immune suppressive microenvironment, which was associated with tumour evolution and a poor prognosis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据