Targeting autophagy can synergize the efficacy of immune checkpoint inhibitors against therapeutic resistance: New promising strategy to reinvigorate cancer therapy
Mehrdad Hashemi,
Elaheh Mohandesi Khosroshahi,
Mahsa Tanha,
Saloomeh Khoushab,
Anahita Bizhanpour,
Farnaz Azizi,
Mahsa Mohammadzadeh,
Arash Matinahmadi,
Zeinab Khazaei Koohpar,
Saba Asadi,
Hengameh Taheri,
Ramin Khorrami,
Marzieh Ramezani Farani,
Mohsen Rashidi,
Mahdi Rezaei,
Eisa Fattah,
Afshin Taheriazam,
Maliheh Entezari
Affiliations
Mehrdad Hashemi
Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Elaheh Mohandesi Khosroshahi
Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Mahsa Tanha
Department of Biological Sciences, University of Alabama, Tuscaloosa, AL, United States
Saloomeh Khoushab
Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Anahita Bizhanpour
Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Farnaz Azizi
Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Mahsa Mohammadzadeh
Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Arash Matinahmadi
Department of Cellular and Molecular Biology, Nicolaus Copernicus University, Torun, Poland
Zeinab Khazaei Koohpar
Department of Cell and Molecular Biology, Faculty of Biological Sciences, Tonekabon Branch, Islamic Azad University, Tonekabon, Iran
Saba Asadi
Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Hengameh Taheri
Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Ramin Khorrami
Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
Marzieh Ramezani Farani
Department of Biological Sciences and Bioengineering, Nano Bio High-Tech Materials Research Center, Inha University, 100 Inha-ro, Michuhol-gu, Incheon, 22212, Republic of Korea
Mohsen Rashidi
Department Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari, Iran; Corresponding author. Department Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Mahdi Rezaei
Health Research Center, Chamran Hospital, Tehran, Iran; Corresponding author.
Eisa Fattah
School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Corresponding author.
Afshin Taheriazam
Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Orthopedics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Corresponding author. Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Maliheh Entezari
Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Corresponding author. Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Immune checkpoints are a set of inhibitory and stimulatory molecules/mechanisms that affect the activity of immune cells to maintain the existing balance between pro- and anti-inflammatory signaling pathways and avoid the progression of autoimmune disorders. Tumor cells can employ these checkpoints to evade immune system. The discovery and development of immune checkpoint inhibitors (ICIs) was thereby a milestone in the area of immuno-oncology. ICIs stimulate anti-tumor immune responses primarily by disrupting co-inhibitory signaling mechanisms and accelerate immune-mediated killing of tumor cells. Despite the beneficial effects of ICIs, they sometimes encounter some degrees of therapeutic resistance, and thereby do not effectively act against tumors. Among multiple combination therapies have been introduced to date, targeting autophagy, as a cellular degradative process to remove expired organelles and subcellular constituents, has represented with potential capacities to overcome ICI-related therapy resistance. It has experimentally been illuminated that autophagy induction blocks the immune checkpoint molecules when administered in conjugation with ICIs, suggesting that autophagy activation may restrict therapeutic challenges that ICIs have encountered with. However, the autophagy flux can also provoke the immune escape of tumors, which must be considered. Since the conventional FDA-approved ICIs have designed and developed to target programmed cell death receptor/ligand 1 (PD-1/PD-L1) as well as cytotoxic T lymphocyte-associated molecule 4 (CTLA-4) immune checkpoint molecules, we aim to review the effects of autophagy targeting in combination with anti-PD-1/PD-L1- and anti-CTLA-4-based ICIs on cancer therapeutic resistance and tumor immune evasion.
