دورية أكاديمية
أعرض في EDS

IRF8 deficiency-induced myeloid-derived suppressor cell promote immune evasion in lung adenocarcinoma.

التفاصيل البيبلوغرافية
العنوان: IRF8 deficiency-induced myeloid-derived suppressor cell promote immune evasion in lung adenocarcinoma.
المؤلفون: Gao Z; Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, Jinan, 250021, Shandong, People's Republic of China., Liu S; Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, Jinan, 250021, Shandong, People's Republic of China., Xiao H; Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, Jinan, 250021, Shandong, People's Republic of China., Li M; Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, Jinan, 250021, Shandong, People's Republic of China., Ren WG; Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, Jinan, 250021, Shandong, People's Republic of China., Xu L; Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, Jinan, 250021, Shandong, People's Republic of China. xl0404@163.com., Peng ZM; Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, Jinan, 250021, Shandong, People's Republic of China. pengzhongmin@sdfmu.edu.cn.
المصدر: Journal of translational medicine [J Transl Med] 2024 Jul 24; Vol. 22 (1), pp. 678. Date of Electronic Publication: 2024 Jul 24.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101190741 Publication Model: Electronic Cited Medium: Internet ISSN: 1479-5876 (Electronic) Linking ISSN: 14795876 NLM ISO Abbreviation: J Transl Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central, 2003-
مواضيع طبية MeSH: Myeloid-Derived Suppressor Cells*/immunology , Adenocarcinoma of Lung*/immunology , Adenocarcinoma of Lung*/genetics , Adenocarcinoma of Lung*/pathology , Interferon Regulatory Factors*/metabolism , Interferon Regulatory Factors*/genetics , Lung Neoplasms*/immunology , Lung Neoplasms*/pathology , Lung Neoplasms*/genetics , Tumor Microenvironment*/immunology, Humans ; Prognosis ; Female ; Gene Expression Regulation, Neoplastic ; Signal Transduction ; Male ; Tumor Escape ; Immune Evasion ; Single-Cell Analysis ; Cell Differentiation
مستخلص: Background: Patients with lung adenocarcinoma (LUAD) have a low response rate to immune checkpoint blockade. It is highly important to explore the tumor immune escape mechanism of LUAD patients and expand the population of patients who may benefit from immunotherapy.
Methods: Based on 954 bulk RNA-seq data of LUAD patients and 15 single-cell RNA-seq data, the relationships between tumor immune dysfunction and exclusion (TIDE) scores and survival prognosis in each patient were calculated and evaluated, and the immune escape mechanism affecting the independent prognosis of LUAD patients was identified. Functional enrichment analysis explored the antitumour immune response and biological behavior of tumor cells among different LUAD groups. Single-cell annotation and pseudotemporal analysis were used to explore the target molecules and immune escape mechanisms of LUAD.
Results: Myeloid-derived suppressor cells (MDSCs) and IRF8 were identified as risk and protective factors for the independent prognosis of LUAD patients, respectively. In the tumor microenvironment of patients with high infiltration of MDSCs, the antitumor immune response is significantly suppressed, while tumor cell division, proliferation, and distant metastasis are significantly enhanced. Single-cell RNA-seq analysis revealed that IRF8 is an important regulator of MDSC differentiation in LUAD myeloid cells. In addition, IRF8 may regulate the differentiation of MDSCs through the IL6-JAK-STAT3 signalling pathway.
Conclusions: IRF8 deficiency impairs the normal development of LUAD myeloid cells and induces their differentiation into MDSCs, thereby accelerating the immune escape of LUAD cells. IRF8-targeted activation to inhibit the formation of MDSCs may be a new target for immunotherapy in LUAD.
(© 2024. The Author(s).)
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معلومات مُعتمدة: 2019JZZY021002 the Major Scientific and Technological Innovation Project of Shandong Province of the Natural Science Foundation of Shandong Province
فهرسة مساهمة: Keywords: IRF8; Immune escape; Lung adenocarcinoma; MDSCs; Tumor microenvironment
المشرفين على المادة: 0 (Interferon Regulatory Factors)
0 (interferon regulatory factor-8)
تواريخ الأحداث: Date Created: 20240725 Date Completed: 20240725 Latest Revision: 20240729
رمز التحديث: 20240730
مُعرف محوري في PubMed: PMC11270856
DOI: 10.1186/s12967-024-05519-7
PMID: 39049031
قاعدة البيانات: MEDLINE
الوصف
تدمد:1479-5876
DOI:10.1186/s12967-024-05519-7