Harnessing TRAIL-Induced Apoptosis Pathway for Cancer Immunotherapy and Associated Challenges

Ehsan Razeghian; Wanich Suksatan; Heshu Sulaiman Rahman; Dmitry O Bokov; Walid Kamal Abdelbasset; Ali Hassanzadeh; Faroogh Marofi; Mahboubeh Yazdanifar; Mostafa Jarahian

doi:10.3389/fimmu.2021.699746

Harnessing TRAIL-Induced Apoptosis Pathway for Cancer Immunotherapy and Associated Challenges

Front Immunol. 2021 Aug 20:12:699746. doi: 10.3389/fimmu.2021.699746. eCollection 2021.

Authors

Ehsan Razeghian¹, Wanich Suksatan², Heshu Sulaiman Rahman^{3

4}, Dmitry O Bokov^{5

6}, Walid Kamal Abdelbasset^{7

8}, Ali Hassanzadeh⁹, Faroogh Marofi¹⁰, Mahboubeh Yazdanifar¹¹, Mostafa Jarahian¹²

Affiliations

¹ Human Genetics Division, Medical Biotechnology Department, National Institute of Genetics Engineering and Biotechnology (NIGEB), Tehran, Iran.
² Faculty of Nursing, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand.
³ Department of Physiology, College of Medicine, University of Suleimanyah, Suleimanyah, Iraq.
⁴ Department of Medical Laboratory Sciences, Komar University of Science and Technology, Sulaimaniyah, Iraq.
⁵ Institute of Pharmacy, Sechenov First Moscow State Medical University, Moscow, Russia.
⁶ Laboratory of Food Chemistry, Federal Research Center of Nutrition, Biotechnology and Food Safety, Moscow, Russia.
⁷ Department of Health and Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al Kharj, Saudi Arabia.
⁸ Department of Physical Therapy, Kasr Al-Aini Hospital, Cairo University, Giza, Egypt.
⁹ Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
¹⁰ Immunology Research Center (IRC), Tabriz University of Medical Sciences, Tabriz, Iran.
¹¹ Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, United States.
¹² Toxicology and Chemotherapy Unit (G401), German Cancer Research Center, Heidelberg, Germany.

Abstract

The immune cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted rapidly evolving attention as a cancer treatment modality because of its competence to selectively eliminate tumor cells without instigating toxicity in vivo. TRAIL has revealed encouraging promise in preclinical reports in animal models as a cancer treatment option; however, the foremost constraint of the TRAIL therapy is the advancement of TRAIL resistance through a myriad of mechanisms in tumor cells. Investigations have documented that improvement of the expression of anti-apoptotic proteins and survival or proliferation involved signaling pathways concurrently suppressing the expression of pro-apoptotic proteins along with down-regulation of expression of TRAILR1 and TRAILR2, also known as death receptor 4 and 5 (DR4/5) are reliable for tumor cells resistance to TRAIL. Therefore, it seems that the development of a therapeutic approach for overcoming TRAIL resistance is of paramount importance. Studies currently have shown that combined treatment with anti-tumor agents, ranging from synthetic agents to natural products, and TRAIL could result in induction of apoptosis in TRAIL-resistant cells. Also, human mesenchymal stem/stromal cells (MSCs) engineered to generate and deliver TRAIL can provide both targeted and continued delivery of this apoptosis-inducing cytokine. Similarly, nanoparticle (NPs)-based TRAIL delivery offers novel platforms to defeat barricades to TRAIL therapeutic delivery. In the current review, we will focus on underlying mechanisms contributed to inducing resistance to TRAIL in tumor cells, and also discuss recent findings concerning the therapeutic efficacy of combined treatment of TRAIL with other antitumor compounds, and also TRAIL-delivery using human MSCs and NPs to overcome tumor cells resistance to TRAIL.

Keywords: combination therapy; mesenchymal stem/stromal cells; nanoparticles; resistance; tumor necrosis factor-related apoptosis-inducing ligand.

Publication types

Review
Retracted Publication

MeSH terms

Animals
Apoptosis / physiology*
Humans
Immunotherapy / methods*
Neoplasms / diet therapy*
Neoplasms / immunology
TNF-Related Apoptosis-Inducing Ligand*

Substances

TNF-Related Apoptosis-Inducing Ligand