Role of soluble human leukocyte antigen-G in virus-associated cancers: A focused minireview

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.