دورية أكاديمية
أعرض في EDS

IRGM is a novel regulator of PD-L1 via promoting S6K1-mediated phosphorylation of YBX1 in hepatocellular carcinoma.

التفاصيل البيبلوغرافية
العنوان: IRGM is a novel regulator of PD-L1 via promoting S6K1-mediated phosphorylation of YBX1 in hepatocellular carcinoma.
المؤلفون: Ru J; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang province, Hangzhou, China., Lu J; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China., Ge J; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang province, Hangzhou, China., Ding B; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China., Su R; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang province, Hangzhou, China., Jiang Y; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang province, Hangzhou, China., Sun Y; General Practice Department, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China., Ma J; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang province, Hangzhou, China., Li Y; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China., Sun J; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang province, Hangzhou, China., Xu G; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China., Tong R; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang province, Hangzhou, China., Zheng S; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang province, Hangzhou, China. Electronic address: shusenzheng@zju.edu.cn., Yang B; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang province, Hangzhou, China. Electronic address: 21518093@zju.edu.cn., Wu J; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China; Key Laboratory of Organ Transplantation, Zhejiang province, Hangzhou, China. Electronic address: drwujian@zju.edu.cn.
المصدر: Cancer letters [Cancer Lett] 2024 Jan 28; Vol. 581, pp. 216495. Date of Electronic Publication: 2023 Nov 21.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Ireland Country of Publication: Ireland NLM ID: 7600053 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7980 (Electronic) Linking ISSN: 03043835 NLM ISO Abbreviation: Cancer Lett Subsets: MEDLINE
أسماء مطبوعة: Publication: Limerick : Elsevier Science Ireland
Original Publication: Amsterdam, Elsevier/North-Holland.
مواضيع طبية MeSH: Antineoplastic Agents*/therapeutic use , Carcinoma, Hepatocellular*/drug therapy , Liver Neoplasms*/drug therapy, Humans ; B7-H1 Antigen/genetics ; B7-H1 Antigen/metabolism ; CD8-Positive T-Lymphocytes ; GTP-Binding Proteins/metabolism ; Phosphorylation ; Tumor Microenvironment ; Y-Box-Binding Protein 1/genetics ; Y-Box-Binding Protein 1/metabolism ; Ribosomal Protein S6 Kinases
مستخلص: Immunity-related GTPase M (IRGM), an Interferon-inducible protein, functions as a pivotal immunoregulator in multiple autoimmune diseases and infection. However, the role of IRGM in hepatocellular carcinoma (HCC) development remains unveiled. Here, we found interferon-γ (IFN-γ) treatment in HCC drastically triggered the expression of IRGM, and the high level of IRGM indicated poor prognosis in HCC patients. Functionally, IRGM promoted the malignant progression of HCC. Single-cell sequencing revealed that IRGM inhibition promoted the infiltration of CD8 + cytotoxic T lymphocytes (CTLs) with significant downregulation of PD-L1 expression in HCC. Furthermore, Immunoprecipitation-Mass Spectrometry assay revealed that IRGM interacted with transcription factor YBX1, which facilitated PD-L1 transcription. Mechanistically, IRGM promoted the interaction of YBX1 and phosphokinase S6K1, increasing phosphorylation and nuclear localization of YBX1, transcription of PD-L1. Additionally, the combination of IRGM inhibition with α-PD1 demonstrated a stronger anti-tumor effect compared to the single application of α-PD1. In summary, IRGM is a novel regulator of PD-L1, which suppresses CD8 + CTLs infiltration and function in HCC, resulting in cancer progression. This study may raise a novel therapeutic strategy combined with immune checkpoint inhibitors (ICIs) against HCC.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: IRGM; Immune therapy; Liver cancer; Programmed death-ligand 1; Tumor microenvironment
المشرفين على المادة: 0 (Antineoplastic Agents)
0 (B7-H1 Antigen)
EC 3.6.1.- (GTP-Binding Proteins)
EC 3.6.1.- (IRGM protein, human)
0 (Y-Box-Binding Protein 1)
0 (YBX1 protein, human)
0 (CD274 protein, human)
EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
تواريخ الأحداث: Date Created: 20231122 Date Completed: 20231220 Latest Revision: 20240123
رمز التحديث: 20240123
DOI: 10.1016/j.canlet.2023.216495
PMID: 37993085
قاعدة البيانات: MEDLINE
الوصف
تدمد:1872-7980
DOI:10.1016/j.canlet.2023.216495