ABSTRACT
@# Lymphocyte-activation gene 3 (LAG-3), also known as CD223, is a 498-amino-acid type I transmembrane protein encoded by LAG-3 gene, which consists of extracellular, transmembrane and intracellular regions.LAG-3 negatively regulates T lymphocyte by binding extracellular domain to ligand, thus avoiding autoimmunitycaused by T cell over-activation. Like programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), LAG-3 is an important immune checkpoint in vivo and plays a balanced regulatory role in human immune system.Tumor cells escape the surveillance of the immune system by over-expressing LAG-3 ligand. With the development in research of immune checkpoints, LAG-3 has become a new generation of immunotherapy targets after PD-1 and CTLA-4. This article reviews the structure and function of LAG-3 and the application of its inhibitors in tumor immunotherapy, in order to provide reference for the further study of LAG-3.
ABSTRACT
Hepatocellular carcinoma (HCC) is the second cause of cancer-related death in the world and is the main cause of death in cirrhotic patients. Unfortunately, the incidence of HCC has grown significantly in the last decade. Curative treatments such as surgery, liver transplantation or percutaneous ablation can only be applied in less than 30% of cases. The multikinase inhibitor sorafenib is the first line therapy for advanced HCC. Regorafenib is the standard of care for second-line patients. However, novel and more specific potent therapeutic approaches for advanced HCC are still needed. The liver constitutes a unique immunological microenvironment, although anti-tumor immunity seems to be feasible with the use of checkpoint inhibitors such as nivolumab. Efficacy may be further increased by combining checkpoint inhibitors or by applying loco-regional treatments. The success of immune checkpoint blockade has renewed interest in immunotherapy in HCC.
El hepatocarcinoma (HCC) es la segunda causa de muerte relacionada con el cáncer en el mundo y es la principal causa de muerte en pacientes cirróticos. Desafortunadamente, la incidencia de HCC ha crecido significativamente en la última década. Los tratamientos curativos como la cirugía, el trasplante de hígado o la ablación solo pueden aplicarse en menos del 30% de los casos. El sorafenib es el tratamiento de primera línea para el HCC avanzado, mientras que el regorafenib se reserva como segunda línea. Sin embargo, todavía son necesarios nuevos enfoques terapéuticos potentes y más específicos para el HCC avanzado. El hígado constituye un microambiente inmunológico único, aunque la inmunidad antitumoral parece ser factible mediante el uso de inhibidores de punto de control como nivolumab. La eficacia puede aumentarse adicionalmente combinando inhibidores de puntos de control inmunitario o aplicando tratamientos loco-regionales. En este sentido, el éxito del uso de anticuerpos monoclonales, que bloquean el control inmunitario, ha renovado el interés en la inmunoterapia para el HCC.
Subject(s)
Humans , Carcinoma, Hepatocellular/drug therapy , Antineoplastic Agents, Immunological/therapeutic use , Immunotherapy/methods , Liver Neoplasms/drug therapy , Antibodies, Monoclonal/therapeutic use , Phenylurea Compounds/therapeutic use , Pyridines/therapeutic use , Clinical Trials as Topic , Sorafenib/therapeutic use , Nivolumab/therapeutic useABSTRACT
Objective:To study the relationship between cytotoxic T lymphocyte antigen 4 (CTLA-4) gene + 49A/G polymorphism and the risk of periodontitis.Methods:A comprehensive literature research was electronically performed to retrieve currently published studies regarding the association of CTLA-4 gene +49A/G polymorphism with periodontitis susceptibility.The individual OR with 95％ CI was pooled to calculate the strength of the association using RevMan 5.2 software.Results:4 out of 18 seached studies satisfied the standard for Meta-analysis.A total of 702 cases and 926 controls were finally included in the Meta-analysis.Overall,no significant association of CTLA-4 gene + 49A/G polymorphism with the risk of periodontitis was observed (P ＞ 0.05).In the subgroup analysis by ethnicity,the results showed a significant association of CTLA-4 gene + 49A/G polymorphism with increased risk of periodontitis in Asian population(P ＜ 0.05) but not in Caucasian population(all P ＞ 0.05).The stratification analysis by subtypes of periodontitis revealed no significant association of the polymorphism with chronic and aggressive periodontitis respectively (all P ＞ 0.05).Conclusion:The present studies suggest that CTLA-4 gene + 49A/G polymorphism may be not associated with the risk of periodontitis in the overall population,but correlated with an increased risk of periodontitis in Asian population.