Cancer Genetics and Epigenetics 2024, Vol.12, No.1, 15-26 http://www.medscipublisher.com/index.php/cge 17 The most common immune checkpoint inhibitors are anti-CTLA-4 antibodies and anti-PD-1/PD-L1 antibodies. CTLA-4 is a molecule that negatively regulates during T cell activation, suppressing T cell activity. Anti-CTLA-4 antibodies can block the binding of CTLA-4 to its ligand, enhancing T cells' ability to attack tumor cells. PD-1 is a molecule expressed on activated T cells' surfaces, and its ligand PD-L1 is often expressed on tumor cell surfaces. The binding of PD-1 to PD-L1 inhibits T cell activity. Anti-PD-1 and anti-PD-L1 antibodies can block the binding between PD-1 and PD-L1, restoring T cell cytotoxicity. Immune checkpoint inhibitors have shown significant success in treating various cancers. They not only improve patient survival rates but also provide enduring treatment effects. However, immune checkpoint inhibitors also have side effects such as immune-related toxicities, including skin inflammation, colitis, and hepatitis. Therefore, close monitoring and management of patients' immune-related side effects are necessary when using immune checkpoint inhibitors. The fundamental principle of immunotherapy is to modulate and enhance the functionality of a patient's immune system to recognize, attack, and eliminate tumor cells. Immune checkpoint inhibitors represent an important immunotherapy method by blocking the function of immune checkpoint molecules to bolster the immune system's ability to target tumor cells. Nevertheless, immunotherapy still faces challenges, including immune resistance and immune-related toxicities. Further research and clinical practice are essential to enhance the efficacy and safety of immunotherapy (Figure 1). Figure 1 Diagnosis and method of endometrial cancer 2 Uterine Endometrial Cancer Immunotherapy Strategies 2.1 Clinical application of PD-1/PD-L1 inhibitors PD-1/PD-L1 inhibitors are a class of drugs targeting immune checkpoint molecules. By interrupting the interaction between programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1), these drugs enhance the immune cells' ability to attack tumor cells. In clinical studies, PD-1/PD-L1 inhibitors have shown significant efficacy in various tumor types, including uterine endometrial cancer. Currently, PD-1/PD-L1 inhibitors have made important strides in clinical research on uterine endometrial cancer. One of the extensively studied PD-1/PD-L1 inhibitors is Pembrolizumab. Pembrolizumab is a high-affinity humanized monoclonal antibody that selectively binds and blocks the interaction between PD-1 and PD-L1. In the treatment of uterine endometrial cancer, Pembrolizumab has demonstrated clear efficacy in several clinical trials (Huvila et al., 2021). A clinical trial named KEYNOTE-028 investigated Pembrolizumab's application in patients with advanced or metastatic uterine endometrial cancer. The results indicated that approximately 20% to 30% of patients treated with Pembrolizumab experienced either partial or complete tumor regression. Furthermore, the study found that PD-L1-positive patients exhibited longer survival periods following Pembrolizumab treatment. Apart from Pembrolizumab, other PD-1/PD-L1 inhibitors such as Nivolumab and Atezolizumab have been under study in clinical trials for uterine endometrial cancer. Nivolumab is a PD-1 inhibitor, and Atezolizumab is a PD-L1 inhibitor. Early study outcomes suggest similar efficacy of these inhibitors in treating uterine endometrial cancer. However, further research is needed to determine the optimal usage and dosage of these drugs.
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