Bin Huang, Keng Chen, Mingjiang Huang, Zhangyong Yin, Wei He, Xuyang Peng, Gongzhi Wu, Jianyang Ding, Congxiong Peng, Xuhui Wu
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引用次数: 0
Abstract
Objectives: The main purpose of this study is to investigate the specific role of SPC25 in the anti-tumor immune process of Natural killer (NK) cells in lung adenocarcinoma (LUAD).
Methods: The differentially expressed gene SPC25 was screened by the Cancer Genome Atlas database. The effect of SPC25 on the anti-tumor immunity of NK cells was evaluated by immunofluorescence, flow cytometry, lactate dehydrogenase kit, and enzyme-linked immunosorbent assay. The influence of SPC25 on glutamine (GLN) metabolism was examined by the GLN metabolism-related kit and Western blot. The interaction between SPC25 and TFDP1 was assessed by luciferase reporter gene detection and ChIP.
Results: SPC25 was overexpressed in LUAD (p < 0.0001), being capable of reducing levels of cytotoxicity and cytokines in NK cells. SPC25 repressed the function of NK cells by activating GLN metabolism (p < 0.0001). Mechanistically, TFDP1 was a transcriptional activator of SPC25. Knocking down TFDP1 hindered GLN metabolism (p < 0.05) and potentiated NK cell killing ability against LUAD cells, while overexpression of SPC25 reversed the effects of TFDP1 knockdown.
Conclusion: This study intended to verify the inhibitory effect of TFDP1 on NK cell anti-tumor immunity by activating SPC25-mediated LUAD glutamine metabolism.
期刊介绍:
Expert Review of Clinical Immunology (ISSN 1744-666X) provides expert analysis and commentary regarding the performance of new therapeutic and diagnostic modalities in clinical immunology. Members of the International Editorial Advisory Panel of Expert Review of Clinical Immunology are the forefront of their area of expertise. This panel works with our dedicated editorial team to identify the most important and topical review themes and the corresponding expert(s) most appropriate to provide commentary and analysis. All articles are subject to rigorous peer-review, and the finished reviews provide an essential contribution to decision-making in clinical immunology.
Articles focus on the following key areas:
• Therapeutic overviews of specific immunologic disorders highlighting optimal therapy and prospects for new medicines
• Performance and benefits of newly approved therapeutic agents
• New diagnostic approaches
• Screening and patient stratification
• Pharmacoeconomic studies
• New therapeutic indications for existing therapies
• Adverse effects, occurrence and reduction
• Prospects for medicines in late-stage trials approaching regulatory approval
• Novel treatment strategies
• Epidemiological studies
• Commentary and comparison of treatment guidelines
Topics include infection and immunity, inflammation, host defense mechanisms, congenital and acquired immunodeficiencies, anaphylaxis and allergy, systemic immune diseases, organ-specific inflammatory diseases, transplantation immunology, endocrinology and diabetes, cancer immunology, neuroimmunology and hematological diseases.