Harnessing the potential of HLA-G in cancer therapy: advances, challenges, and prospects

作者：Siyuan Wang, Jiaxin Wang, Yu Xia, Le Zhang, Yueqiang Jiang, Man Liu, Qinglei Gao, Cuntai Zhang · 发表于：Journal of Translational Medicine · 年份：2024 · DOI：10.1186/s12967-024-04938-w · 被引用次数：42 · 研究领域：Reproductive System and Pregnancy、Immunotherapy and Immune Responses、Ovarian cancer diagnosis and treatment

Abstract Immune checkpoint blockades have been prized in circumventing and ablating the impediments posed by immunosuppressive receptors, reaching an exciting juncture to be an innovator in anticancer therapy beyond traditional therapeutics. Thus far, approved immune checkpoint blockades have principally targeted PD-1/PD-L1 and CTLA-4 with exciting success in a plethora of tumors and yet are still trapped in dilemmas of limited response rates and adverse effects. Hence, unveiling new immunotherapeutic targets has aroused immense scientific interest in the hope of expanding the clinical application of immune checkpoint blockades to scale new heights. Human leukocyte antigen-G (HLA-G), a non-classical major histocompatibility complex (MHC) class I molecule, is enriched on various malignant cells and is involved in the hindrance of immune effector cells and the facilitation of immunosuppressive cells. HLA-G stands out as a crucial next-generation immune checkpoint showing great promise for the benefit of cancer patients. Here, we provide an overview of the current understanding of the expression pattern and immunological functions of HLA-G, as well as its interaction with well-characterized immune checkpoints. Since HLA-G can be shed from the cell surface or released by various cells as free soluble HLA-G (sHLA-G) or as part of extracellular vesicles (EVs), namely HLA-G-bearing EVs (HLA-G EV ), we discuss the potential of sHLA-G and HLA-G EV as predictive biomarkers. This review...