지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2024.9
- 수록면
- 426 - 436 (11page)
- DOI
- 10.3343/alm.2023.0443
이용수
초록· 키워드
오류제보하기
Background: Metformin, a drug prescribed for patients with type 2 diabetes, has potential efficacy in enhancing antitumor immunity; however, the detailed underlying mechanisms remain to be elucidated. Therefore, we aimed to identify the inhibitory molecular mechanisms of metformin on programmed death ligand 1 (PD-L1) expression in cancer cells and programmed death 1 (PD-1) expression in immune cells.
Methods: We employed a luciferase reporter assay, quantitative real-time PCR, immunoblotting analysis, immunoprecipitation and ubiquitylation assays, and a natural killer (NK) cell-mediated tumor cell cytotoxicity assay. A mouse xenograft tumor model was used to evaluate the effect of metformin on tumor growth, followed by flow-cytometric analysis using tumor-derived single-cell suspensions.
Results: Metformin decreased AKT-mediated β-catenin S552 phosphorylation and subsequent β-catenin transactivation in an adenosine monophosphate-activated protein kinase (AMPK) activation-dependent manner, resulting in reduced CD274 (encoding PD-L1) transcription in cancer cells. Tumor-derived soluble factors enhanced PD-1 protein stability in NK and T cells via dissociation of PD-1 from ubiquitin E3 ligases and reducing PD-1 polyubiquitylation.
Metformin inhibited the tumor-derived soluble factor-reduced binding of PD-1 to E3 ligases and PD-1 polyubiquitylation, resulting in PD-1 protein downregulation in an AMPK activation-dependent manner. These inhibitory effects of metformin on both PD-L1 and PD-1 expression ameliorated cancer-reduced cytotoxic activity of immune cells in vitro and decreased tumor immune evasion and growth in vivo.
Conclusions: Metformin blocks both PD-L1 and PD-1 within the tumor microenvironment.
This study provided a mechanistic insight into the efficacy of metformin in improving immunotherapy in human cancer.
목차
등록된 정보가 없습니다.
참고문헌 (0)
참고문헌 신청함께 읽어보면 좋을 논문
논문 유사도에 따라 DBpia 가 추천하는 논문입니다. 함께 보면 좋을 연관 논문을 확인해보세요!
-
Enhanced Anti-tumor Reactivity of Cytotoxic T Lymphocytes Expressing PD-1 Decoy
Immune Network
2016 .04
-
Overexpression of PD-L1 and PD-L2 Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma
Cancer Research and Treatment
2017 .01
-
Peripheral Blood Immune Cell-based Biomarkers in Anti-PD-1/PD-L1 Therapy
Immune Network
2020 .02
-
PD-1: A Negative Regulator of Phagocytosis by Tumour-Associated Macrophages in Colon Cancer
JOURNAL OF BACTERIOLOGY AND VIROLOGY
2019 .12
-
PD-L1 Testing in Non-small Cell Lung Cancer: Past, Present, and Future
Journal of Pathology and Translational Medicine
2019 .01
-
PD-L1 Expression and Combined Status of PD-L1/PD-1–Positive Tumor Infiltrating Mononuclear Cell Density Predict Prognosis in Glioblastoma Patients
Journal of Pathology and Translational Medicine
2017 .01
-
Enhanced anti-tumor immunity of vaccine combined with anti-PD-1 antibody in a murine bladder cancer model
Investigative and Clinical Urology
2023 .01
-
Effect of Platinum-Based Chemotherapy on PD-L1 Expression on Tumor Cells in Non-small Cell Lung Cancer
Cancer Research and Treatment
2019 .01
-
Advantages of robotic PD over laparoscopic PD
Annals of Hepato-Biliary-Pancreatic Surgery
2022 .12
-
Association between PD-L1 and HPV Status and the Prognostic Value of PD-L1 in Oropharyngeal Squamous Cell Carcinoma
Cancer Research and Treatment
2016 .01
-
Drug-loaded microbubble delivery system to enhance PD-L1 blockade immunotherapy with remodeling immune microenvironment
생체재료학회지
2023 .03
-
Analysis of the Expression and Regulation of PD-1 Protein on the Surface of Myeloid-Derived Suppressor Cells (MDSCs)
Biomolecules & Therapeutics(구 응용약물학회지)
2019 .01
-
Interpretation of PD-L1 expression in gastric cancer: summary of a consensus meeting of Korean gastrointestinal pathologists
Journal of Pathology and Translational Medicine
2024 .05
-
Development of genetically humanized PD-1 mice capable of evaluating preclinical studies of PD-1 immuno-oncology agents
한국실험동물학회 학술발표대회 논문집
2020 .07
-
Dysphagia Requiring Medical Attention in Parkinson’s Disease: A Korean Population-Based Study
Journal of Korean Medical Science
2023 .04
-
Evaluation of circulating PD-1 and PD-L1 as diagnostic biomarkers in dogs with tumors
Journal of Veterinary Science
2021 .09
-
Baseline Serum Interleukin-6 Levels Predict the Response of Patients with Advanced Non-small Cell Lung Cancer to PD-1/PD-L1 Inhibitors
Immune Network
2020 .06
-
Programmed death-ligand 1 expression and its correlation with clinicopathological parameters in gallbladder cancer
Journal of Pathology and Translational Medicine
2020 .01
-
Immune Checkpoint Programmed Cell Death Protein-1 (PD-1) Expression on Bone Marrow T Cell Subsets in Patients With Plasma Cell Myeloma
Annals of Laboratory Medicine
2021 .01
-
Programmed cell death-ligand 1 assessment in urothelial carcinoma: prospect and limitation
Journal of Pathology and Translational Medicine
2021 .01
최근 본 자료
댓글(0)
0