Gastrointestinal cancer stem cells as targets for innovative immunotherapy

World J Gastroenterol. 2020 Apr 14;26(14):1580-1593. doi: 10.3748/wjg.v26.i14.1580.


The role of cancer stem cells in gastrointestinal cancer-associated death has been widely recognized. Gastrointestinal cancer stem cells (GCSCs) are considered to be responsible for tumor initiation, growth, resistance to cytotoxic therapies, recurrence and metastasis due to their unique properties. These properties make the current therapeutic trials against GCSCs ineffective. Moreover, recent studies have shown that targeting stem cell surface markers or stemness associated pathways might have an additional off-target effect on the immune system. Recent advances in oncology and precision medicine have opened alternative therapeutic strategies in the form of cancer immunotherapy. This approach differs from classical anti-cancer therapy through its mechanism of action involving the activation and use of a functional immune system against tumor cells, instead of aiming physically destruction of cancer cells through radio- or chemotherapy. New immunological approaches for GCSCs targeting involve the use of different immune cells and various immune mechanisms like targeting specific surface antigens, using innate immune cells like the natural killer and T cells, T-cell chimeric antigen receptor technology, dendritic cell vaccine, or immune checkpoint inhibitors. In this respect, better understandings of immune regulatory mechanisms that govern anti-tumor response bring new hope in obtaining long-term remission for cancer therapy.

Keywords: CAR-T; Cancer stem cells; Dendritic cells vaccines; Gastrointestinal cancer; Immune checkpoints inhibitors; Immunotherapy.

Publication types

  • Review

MeSH terms

  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / immunology
  • Biomarkers, Tumor / metabolism
  • Cancer Vaccines / administration & dosage
  • Combined Modality Therapy / methods
  • Dendritic Cells / immunology
  • Drug Resistance, Neoplasm / immunology
  • Gastrointestinal Neoplasms / immunology
  • Gastrointestinal Neoplasms / pathology
  • Gastrointestinal Neoplasms / therapy*
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunity, Innate / drug effects
  • Immunity, Innate / immunology*
  • Immunotherapy / methods*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / transplantation
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / prevention & control*
  • Neoplastic Stem Cells / immunology*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Receptors, Chimeric Antigen / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation
  • Tumor Escape / drug effects
  • Tumor Escape / immunology


  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Cancer Vaccines
  • Immune Checkpoint Inhibitors
  • Receptors, Chimeric Antigen