Understanding tumour cell heterogeneity and its implication for immunotherapy in liver cancer using single-cell analysis

J Hepatol. 2021 Mar;74(3):700-715. doi: 10.1016/j.jhep.2020.11.036. Epub 2020 Nov 30.

Abstract

Over the last decade, precision medicine and immunotherapeutic approaches have become increasingly popular in oncology. Early clinical trials reported promising results, but response rates in phase III clinical trials have been suboptimal. Knowledge gained from subsequent translational studies indicates the importance of targeting the tumour microenvironment to overcome resistance to immunotherapy. In this era of precision medicine, it is crucial to consider inter- as well as intratumoural heterogeneity. Single-cell analysis is a cutting-edge technology that enables us to better define the tumour cell community and to identify potential targets for immunotherapy or combination treatments. This review focuses on single-cell analysis in the context of immunotherapy in liver cancer, including the rationale behind studying hepatocellular carcinoma biology at a single-cell level. Single-cell technologies have the potential to revolutionise our understanding of resistance mechanisms and to guide drug discovery efforts, leading to further advances in personalised medicine.

Keywords: Cancer; Hepatocellular carcinoma; Heterogeneity; Liver; Omics; Sequencing; Single-cell analysis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Combined Modality Therapy / methods
  • Genetic Heterogeneity*
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Immunotherapy / methods*
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Precision Medicine / methods
  • Single-Cell Analysis / methods*
  • Transcriptome / genetics*
  • Treatment Outcome
  • Tumor Microenvironment / immunology

Substances

  • Immune Checkpoint Inhibitors