The emerging and challenging role of PD-L1 in patients with gynecological cancers: An updating review with clinico-pathological considerations

Over recent years, there has been significant progress in the development of immunotherapeutic molecules designed to block the PD-1/PD-L1 axis. These molecules have demonstrated their ability to enhance the immune response by prompting T cells to identify and suppress neoplastic cells. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes, and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in gynecological malignancies is extremely variable based on tumor stage and molecular subtypes. As a result, a class of monoclonal antibodies targeting the PD-1 receptor and PD-L1, known as immune checkpoint inhibitors, has found successful application in clinical settings. In clinical practice, the standard method for identifying suitable candidates for immune checkpoint inhibitor therapy involves immunohistochemical assessment of PD-L1 expression in neoplastic tissues. The most commonly used PD-L1 assays in clinical trials are SP142, 28-8, 22C3, and SP263, each of which has been rigorously validated on specific platforms. Gynecologic cancers encompass a wide spectrum of malignancies originating from the ovaries, uterus, cervix, and vulva. These neoplasms have shown variable response to immunotherapy which appears to be influenced by genetic and protein expression profiles, including factors such as mismatch repair status, tumor mutational burden, and checkpoint ligand expression. In the present paper, an extensive review of PD-L1 expression in various gynecologic cancer types is discussed, providing a guide for their pathological assessment and reporting.