Mehrdad Fathi1, Simin Bahmanpour2, Asal Barshidi2, Hossein Rasouli2, Fariba Karoon Kiani2, Armin Mahmoud Salehi Khesht2, Sepideh Izadi3, Bentolhoda Rashidi2, Shiva Kermanpour2, Roya Mokhtarian2, Vahid Karpisheh3, Hadi Hassannia4, Hamed Mohammadi5, Ali Jalili6, Farhad Jadidi-Niaragh7. 1. Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran; Cancer and Immunology Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran; Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran. 2. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 3. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. 4. Immunogenetic Research Center, Faculty of Medicine and Amol Faculty of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran. 5. Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran. 6. Cancer and Immunology Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran; Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran. Electronic address: Ali130@gmail.com. 7. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: jadidif@tbzmed.ac.ir.
Abstract
PURPOSE: T-cell immunoglobulin and ITIM domain (TIGIT) is an immune checkpoint that is overexpressed on both immune cells and some cancer cells. TIGIT can alter the anti-tumor responses inside the tumor microenvironment. Hypoxia-inducible factor 1-alpha (HIF-1α) plays a significant role in the TME and involves suppressing the anti-tumor responses. Under hypoxic conditions, HIF-1α can enhance the expression of different immune checkpoints. Accordingly, hypoxic TME and TIGIT overexpression cause cancer development. Thus, we decided to inhibit tumor cell expansion by inhibiting TIGIT and HIF-1α molecules and discovering the relationship between TIGIT and HIF-1α. METHODS: In this research, we utilized superparamagnetic iron oxide-based NPs (SPIONs) combined with chitosan lactate (CL) and folic acid (FA) nanoparticles (NPs) loaded with TIGIT-siRNA and HIF-1α- siRNA for suppressing TIGIT and HIF-1α in tumor cells and evaluated the consequences of this treatment strategy on tumor growth, apoptosis, and metastasis. RESULTS: The results showed that cancer cells treated with TIGIT and HIF-1α siRNA-loaded SPIONs-CL-FA NPs, strongly suppressed the TIGIT and HIF-1α expression, colony formation ability, angiogenesis, and the growth rate of cancer cells. CONCLUSIONS: Present data suggest the combination treatment of TIGIT and HIF-1α as a novel treatment strategy against colorectal and breast cancer, but more researches are required to realize the complete role of TIGIT and HIF-1α inside the TME.
PURPOSE: T-cell immunoglobulin and ITIM domain (TIGIT) is an immune checkpoint that is overexpressed on both immune cells and some cancer cells. TIGIT can alter the anti-tumor responses inside the tumor microenvironment. Hypoxia-inducible factor 1-alpha (HIF-1α) plays a significant role in the TME and involves suppressing the anti-tumor responses. Under hypoxic conditions, HIF-1α can enhance the expression of different immune checkpoints. Accordingly, hypoxic TME and TIGIT overexpression cause cancer development. Thus, we decided to inhibit tumor cell expansion by inhibiting TIGIT and HIF-1α molecules and discovering the relationship between TIGIT and HIF-1α. METHODS: In this research, we utilized superparamagnetic iron oxide-based NPs (SPIONs) combined with chitosan lactate (CL) and folic acid (FA) nanoparticles (NPs) loaded with TIGIT-siRNA and HIF-1α- siRNA for suppressing TIGIT and HIF-1α in tumor cells and evaluated the consequences of this treatment strategy on tumor growth, apoptosis, and metastasis. RESULTS: The results showed that cancer cells treated with TIGIT and HIF-1α siRNA-loaded SPIONs-CL-FA NPs, strongly suppressed the TIGIT and HIF-1α expression, colony formation ability, angiogenesis, and the growth rate of cancer cells. CONCLUSIONS: Present data suggest the combination treatment of TIGIT and HIF-1α as a novel treatment strategy against colorectal and breast cancer, but more researches are required to realize the complete role of TIGIT and HIF-1α inside the TME.
Authors: S González-Ochoa; M C Tellez-Bañuelos; A S Méndez-Clemente; A Bravo-Cuellar; G Hernández Flores; L A Palafox-Mariscal; J Haramati; E J Pedraza-Brindis; K Sánchez-Reyes; P C Ortiz-Lazareno Journal: J Immunol Res Date: 2022-04-12 Impact factor: 4.493