Overview of Immune Checkpoint Inhibitors in Gynecological Cancer Treatment

Abstract

In the last ten years, clinical oncology has been revolutionized by the introduction of oncological immunotherapy, mainly in the form of immune checkpoint inhibitors (ICIs) that transformed the standard of care of several advanced solid malignancies. Using ICIs for advanced gynecological cancers has yielded good results, especially for endometrial cancer. In ovarian or cervical cancer, combining ICIs with other established agents has shown some promise. Concurrently with the clinical development of ICIs, biomarkers that predict responses to such therapy have been discovered and used in clinical trials. The translation of these biomarkers to clinical practice was somewhat hampered by lacking assay standardization and non-comprehensive reporting of biomarker status in trials often performed on a small number of gynecological cancer patients. We can expect increased use of ICIs combined with other agents in gynecological cancer in the near future. This will create a need for reliable response prediction tools, which we believe will be based on biomarker, clinical, and tumor characteristics. In this article, we review the basic biology of ICIs and response prediction biomarkers, as well as the latest clinical trials that focus on subgroup effectiveness based on biomarker status in gynecological cancer patients.

Integrated in silico analysis of LRP2 mutations to immunotherapy efficacy in pan-cancer cohort

“…However, the mechanism by which LRP2 enhanced immunotherapy response remained unclear. One reasonable explanation is that neo-antigens that accompany genetic mutations facilitate the recognition and killing of immune cells to tumor cell [44]. Meanwhile, dMMR/MSI-H tumors also have the ability to produce a plethora of immunogenic neoantigens on the MHC, recruiting T-cells within the tumor and priming T-cells to recognize them [45].…”

Excavation of Molecular Subtypes of Endometrial Cancer Based on DNA Methylation

“…Most clinically used drugs stop the mechanisms that dampen immune response; these drugs are called immune checkpoint inhibitors (ICIs). Among gynecological diseases, ICIs are one of the most effective methods to treat endometrial cancer [ 32 ]. In this study, we compared the expression levels of immune checkpoints between the three clusters.…”

Immune checkpoint inhibitors in cervical cancer: Current status and research progress

“…Immune checkpoints play a key role in the immune escape of tumor cells. Immune checkpoints are immunosuppressive molecules that function as negative regulators to regulate the immune response, which are important pathways for the immune system to avoid self-immune response ( 12 , 13 ). The most studied immune checkpoints in cervical cancer include programmed death 1/programmed death ligand-1 (PD-1/PD-L1) and cytotoxic T lymphocyte antigen (CTLA-4).…”

“…CTLA-4 protein is a T cell surface receptor constitutively expressed on regulatory T cells (Tregs) and binds to its ligands (CD80 and CD86). CTLA-4 is believed to inhibit T-cell proliferation by blunting the antigen presenting cells thus providing negative feedback in the immune response ( 12 , 18 ).Other immune checkpoints being studied in cervical cancer include indoleamine 2,3-dioxygenase 1 (IDO1), lymphocyte-activation gene 3 (LAG3), T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), glucocorticoid-induced TNFR-related protein (GITR), and T cell immunoreceptor with Ig and ITIM domains (TIGHT). IDO1 is a rate-limiting metabolic enzyme overexpressed in T cells of tumor patients.…”