UBTF facilitates acute myeloid leukemia development and immune escape via PD-L1 regulation

IF 4.8 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-03-13 DOI:10.1016/j.intimp.2025.114433

Chunxia Yang , Junzhao Wan , Yan Wang , Ying Yang , Yunsheng Ran , Fenli Zhang , Man Zhou , Ping Liu , Qian Kang , Dan Ma , Xiaoyan Yang

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引用次数: 0

Abstract

UBTF has been implicated in the development of multiple cancers, yet its specific biological function in acute myeloid leukemia (AML) remains unclear. This study utilized expression profiles and clinical data from The Cancer Genome Atlas (TCGA) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) databases, with UBTF expression data obtained from the GEPIA database. Analysis via the R software package CIBERSORT explored immune cell infiltration levels under different UBTF expression levels. LASSO Cox analysis with optimized penalty parameters identified genes associated with survival outcomes, leading to the construction of a prognostic risk model using multivariate Cox regression analysis. Prognostic significance was evaluated and validated through Kaplan-Meier survival analysis and receiver operating characteristic curve analysis. Experimental validation using stable AML cell lines with UBTF overexpression or knockdown, transcriptome sequencing, and a CD8⁺ T cell killing assay were performed. Ultimately, in vivo experimental validation was conducted. Results revealed that UBTF is overexpressed in AML compared to normal tissues and correlates with poor clinical prognosis. UBTF overexpression is associated with increased expression of PD-L1 (CD274) and immune cell infiltration, suggesting its role in promoting AML progression via PD-L1 (CD274)-mediated immune evasion. These findings highlight UBTF as a potential prognostic biomarker and a novel therapeutic target for tumor immunotherapy in AML.

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.