HLA-G - evolvement from a trophoblast specific marker to a checkpoint molecule in cancer, a narrative review about the specific role in breast- and gynecological cancer

Abstract

Human leukocyte antigen G (HLA-G) is known as a non-classical molecule of the major histocompatibility complex class Ib and downregulates the mother's immune response against the fetus during pregnancy, thereby generating immune tolerance. Due to the latter effect, HLA-G is also referred to as an immune checkpoint molecule. Originally identified on extravillous trophoblasts, HLA-G is already known to induce immune tolerance at various stages of the immune response, for example through cell differentiation and proliferation, cytolysis and cytokine secretion. Because of these functions, HLA-G is involved in various processes of cancer progression, but a comprehensive review of the role of HLA-G in gynecologic cancers is lacking. Therefore, this review focuses on the existing knowledge of HLA-G in ovarian cancer, endometrial cancer, cervical cancer and breast cancer. HLA-G is predominantly expressed in cancer tissues adjacent to the extravillous trophoblast. Therefore, modulating its expression in the cancer target tissues of cancer patients could be a potential therapeutic approach to treat these diseases.