Rahmati M, Moghtaderi H, Mohammadi S, Al-Harrasi A. Aryl hydrocarbon receptor dynamics in esophageal squamous cell carcinoma: From immune modulation to therapeutic opportunities. World J Exp Med 2024; 14(3): 96269 [DOI: 10.5493/wjem.v14.i3.96269]
Corresponding Author of This Article
Ahmed Al-Harrasi, PhD, Full Professor, Natural and Medical Sciences Research Center, University of Nizwa, Birkat Al Mauz, PO Box 33, Postal Code 616, Nizwa, Oman. aharrasi@unizwa.edu.om
Research Domain of This Article
Immunology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Exp Med. Sep 20, 2024; 14(3): 96269 Published online Sep 20, 2024. doi: 10.5493/wjem.v14.i3.96269
Aryl hydrocarbon receptor dynamics in esophageal squamous cell carcinoma: From immune modulation to therapeutic opportunities
Mina Rahmati, Hassan Moghtaderi, Saeed Mohammadi, Ahmed Al-Harrasi
Mina Rahmati, Biotechnology Research Center, Pasteur Institute of Iran, Tehran 1316943551, Tehran, Iran
Hassan Moghtaderi, Saeed Mohammadi, Ahmed Al-Harrasi, Natural and Medical Sciences Research Center, University of Nizwa, Nizwa 616, Ad Dakhiliyah, Oman
Co-first authors: Mina Rahmati and Hassan Moghtaderi.
Co-corresponding authors: Saeed Mohammadi and Ahmed Al-Harrasi.
Author contributions: Rahmati M and Moghtaderi H reviewed the literature, prepared information, and drafted the manuscript; Mohammadi S and Al-Harrasi A conceptualized the review, proposed the title, and provided critical reviews; All authors have read and approved the final manuscript. Rahmati M and Moghtaderi H reviewed relevant literature, gathered essential information, and drafted the initial version of the manuscript. Rahmati M organized the data and ensured the integration of comprehensive and relevant studies into the review. Moghtaderi H synthesized the gathered information and contributed significantly to the initial manuscript draft. Mohammadi S and Al-Harrasi A conceptualized the overall scope of the review article and proposed the title. Mohammadi S offered essential perspectives that maintained the manuscript's logical flow and improved its scientific precision during the revision stages. Al-Harrasi A conducted extensive reviews and contributed to revising the content to meet high academic standards. Both Rahmati M and Moghtaderi H made crucial contributions towards the completion of the review, qualifying as co-first authors. Both Mohammadi S and Al-Harrasi A played important and essential roles in the conceptual design, critical review, and manuscript preparation as co-corresponding authors. Mohammadi S supervised the entire review process, provided continuous oversight, and ensured the manuscript's coherence. Al-Harrasi A contributed significantly to the critical review, enhancing the manuscript's quality and accuracy. This collaboration between Mohammadi S and Al-Harrasi A was essential for the successful completion and publication of this manuscript. Their combined efforts in conceptual design, critical review, and supervision were crucial for maintaining the manuscript's high standards and academic integrity.
Conflict-of-interest statement: All the authors declare that there are no conflicts of interest to disclose.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ahmed Al-Harrasi, PhD, Full Professor, Natural and Medical Sciences Research Center, University of Nizwa, Birkat Al Mauz, PO Box 33, Postal Code 616, Nizwa, Oman. aharrasi@unizwa.edu.om
Received: May 1, 2024 Revised: May 26, 2024 Accepted: June 14, 2024 Published online: September 20, 2024 Processing time: 119 Days and 21.3 Hours
Abstract
Esophageal squamous cell carcinoma (ESCC) is a substantial global health burden. Immune escape mechanisms are important in ESCC progression, enabling cancer cells to escape the surveillance of the host immune system. One key player in this process is the Aryl Hydrocarbon Receptor (AhR), which influences multiple cellular processes, including proliferation, differentiation, metabolism, and immune regulation. Dysregulated AhR signaling participates in ESCC development by stimulating carcinogenesis, epithelial-mesenchymal transition, and immune escape. Targeting AhR signaling is a potential therapeutic approach for ESCC, with AhR ligands showing efficacy in preclinical studies. Additionally, modification of AhR ligands and combination therapies present new opportunities for therapeutic intervention. This review aims to address the knowledge gap related to the role of AhR signaling in ESCC pathogenesis and immune escape.
Core Tip: Esophageal squamous cell carcinoma (ESCC) utilizes immune escape mechanisms, including major histocompatibility complex downregulation and immune checkpoint manipulation, enhancing tumor progression. The aryl hydrocarbon receptor (AhR), crucial in health and disease, significantly influences ESCC development and immune evasion through carcinogenic pathways. AhR activation triggers proliferation, inhibits apoptosis, and induces epithelial-mesenchymal transition. Moreover, AhR suppresses effector T cells and enrolls immunosuppressive myeloid cells. Therapeutic AhR targeting with AhR ligands showed promise in inhibiting tumor growth, controlling the immune microenvironment, and enhancing treatment efficacy. Combining AhR-targeted therapies with conventional treatments or dietary interventions has the potential to improve ESCC patient outcomes.
