Bouayad A. Role of soluble human leukocyte antigen-G in virus-associated cancers: A focused minireview. World J Virol 2026; 15(2): 120048 [DOI: 10.5501/wjv.v15.i2.120048]
Corresponding Author of This Article
Abdellatif Bouayad, MD, Associate Professor, Department of Immunology, Faculty of Medicine and Pharmacy of Oujda, Mohammed First University, Hay al Hikma, Oujda 4867, Oriental, Morocco. abdellatifbouayad@hotmail.fr
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Immunology
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review-article
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Bouayad A. Role of soluble human leukocyte antigen-G in virus-associated cancers: A focused minireview. World J Virol 2026; 15(2): 120048 [DOI: 10.5501/wjv.v15.i2.120048]
World J Virol. Jun 25, 2026; 15(2): 120048 Published online Jun 25, 2026. doi: 10.5501/wjv.v15.i2.120048
Role of soluble human leukocyte antigen-G in virus-associated cancers: A focused minireview
Abdellatif Bouayad
Abdellatif Bouayad, Department of Immunology, Faculty of Medicine and Pharmacy of Oujda, Mohammed First University, Oujda 4867, Oriental, Morocco
Author contributions: Bouayad A wrote, designed, and approved the minireview manuscript.
Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article.
Corresponding author: Abdellatif Bouayad, MD, Associate Professor, Department of Immunology, Faculty of Medicine and Pharmacy of Oujda, Mohammed First University, Hay al Hikma, Oujda 4867, Oriental, Morocco. abdellatifbouayad@hotmail.fr
Received: February 13, 2026 Revised: March 8, 2026 Accepted: April 14, 2026 Published online: June 25, 2026 Processing time: 125 Days and 16.9 Hours
Abstract
Soluble human leukocyte antigen-G (sHLA-G), a non-classical major histocompatibility complex class I molecule, arises either through proteolytic cleavage of membrane-bound isoforms or via secretion of soluble isoforms. sHLA-G exerts potent immunosuppressive effects, facilitating immune escape of cancer cells within the tumor microenvironment by inhibiting the cytotoxic activity of natural killer cells, cytotoxic T lymphocytes, and other immune effectors. Emerging evidence indicates that aberrant expression of sHLA-G contributes to tumor progression in virus-associated malignancies, including human papillomavirus-driven cervical cancer and hepatitis B virus/hepatitis C virus-related hepatocellular carcinoma. sHLA-G is detectable in various body fluids, including plasma and serum, highlighting its potential as both a diagnostic and prognostic biomarker as well as a therapeutic target.
Core Tip: Increased soluble human leukocyte antigen-G (sHLA-G) levels are consistently associated with poor prognosis in hepatitis C virus/hepatitis B virus -related hepatocellular carcinoma and human papillomavirus-driven cervical cancer, underscoring its potential as a diagnostic and prognostic biomarker. High-risk human papillomavirus oncoproteins (E6 and E7) and hepatitis C virus proteins (core protein and nonstructural protein 3) may contribute to increased sHLA-G levels through cytokine-mediated immunosuppressive signalling pathways. The mechanisms by which sHLA-G-immunoglobulin-like transcript 2/immunoglobulin-like transcript 4 interactions modulate immune suppression in these virus-driven cancers remain incompletely understood. sHLA-G isoforms are primarily detected in plasma and other biological fluids using sandwich enzyme-linked immunosorbent assays, providing a reliable method for both clinical and research applications.
