Immunotherapy for targeting cancer stem cells in hepatocellular carcinoma

Theranostics. 2021 Jan 19;11(7):3489-3501. doi: 10.7150/thno.54648. eCollection 2021.

Abstract

The rapid development and remarkable success of checkpoint inhibitors have provided significant breakthroughs in cancer treatment, including hepatocellular carcinoma (HCC). However, only 15-20% of HCC patients can benefit from checkpoint inhibitors. Cancer stem cells (CSCs) are responsible for recurrence, metastasis, and local and systemic therapy resistance in HCC. Accumulating evidence has suggested that HCC CSCs can create an immunosuppressive microenvironment through certain intrinsic and extrinsic mechanisms, resulting in immune evasion. Intrinsic evasion mechanisms mainly include activation of immune-related CSC signaling pathways, low-level expression of antigen presenting molecules, and high-level expression of immunosuppressive molecules. External evasion mechanisms are mainly related to HBV/HCV infection, alcoholic/nonalcoholic steatohepatitis, hypoxia stimulation, abnormal angiogenesis, and crosstalk between CSCs and immune cells. A better understanding of the complex mechanisms of CSCs involved in immune evasion will contribute to therapies for HCC. Here we will outline the detailed mechanisms of immune evasion for CSCs, and provide an overview of the current immunotherapies targeting CSCs in HCC.

Keywords: cancer stem cells; hepatocellular carcinoma; immune evasion; immunotherapy; targeting.

Publication types

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

MeSH terms

  • Antigen Presentation / drug effects
  • Antineoplastic Agents, Immunological / therapeutic use
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Fatty Liver / genetics
  • Fatty Liver / immunology
  • Fatty Liver / pathology
  • Fatty Liver / therapy
  • Gene Expression Regulation, Neoplastic
  • Hepatitis B / genetics
  • Hepatitis B / immunology
  • Hepatitis B / pathology
  • Hepatitis B / therapy
  • Hepatitis C / genetics
  • Hepatitis C / immunology
  • Hepatitis C / pathology
  • Hepatitis C / therapy
  • Humans
  • Immunologic Factors / therapeutic use
  • Immunotherapy / methods
  • Liver Neoplasms / genetics
  • Liver Neoplasms / immunology
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / immunology
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy*
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / immunology
  • Neoplastic Stem Cells / pathology
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / prevention & control
  • Signal Transduction
  • Tumor Escape / drug effects*
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • Antineoplastic Agents, Immunological
  • Immunologic Factors
  • Neoplasm Proteins