Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2020; 26(14): 1580-1593
Published online Apr 14, 2020. doi: 10.3748/wjg.v26.i14.1580
Gastrointestinal cancer stem cells as targets for innovative immunotherapy
Mihaela Chivu-Economescu, Laura G Necula, Lilia Matei, Denisa Laura Dragu, Ana I Neagu, Irina Alexiu, Coralia Bleotu, Carmen Cristina Diaconu
Mihaela Chivu-Economescu, Laura G Necula, Lilia Matei, Denisa Laura Dragu, Ana I Neagu, Irina Alexiu, Coralia Bleotu, Carmen Cristina Diaconu, Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
Laura G Necula, Nicolae Cajal Institute, Titu Maiorescu University, Bucharest 040441, Romania
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Supported by the Romanian National Authority for Scientific Research and Innovation, CNCS– UEFISCDI, No. PN-III-P4-ID-PCCF2016-0158.
Conflict-of-interest statement: Authors declare no potential conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Mihaela Chivu-Economescu, PhD, Senior Researcher, Department of Cellular and Molecular Pathology, Stefan S Nicolau Institute of Virology, 285 Mihai Bravu Ave, Bucharest 030304, Romania.
Received: December 13, 2019
Peer-review started: December 13, 2019
First decision: January 16, 2020
Revised: January 22, 2020
Accepted: March 14, 2020
Article in press: March 14, 2020
Published online: April 14, 2020

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: Immunotherapy, Gastrointestinal cancer, Cancer stem cells, CAR-T, Dendritic cells vaccines, Immune checkpoints inhibitors

Core tip: Cancer immunotherapy has emerged in recent years as an alternative to classical anti-tumor therapy. It involves the activation of the host immune system in the fight against tumor cells, including cancer stem cells, which are responsible for tumor maintenance, relapse, and metastasis. Here we discuss the different forms of immunotherapy for gastrointestinal cancer stem cells targeting such as using monoclonal antibodies against surface antigens, generation of effector natural killer cells and T cells genetic engineered to target tumor antigens, dendritic vaccines, and immune checkpoints inhibitors.