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IL4I1信息

英文名称:L-amino-acid oxidase
中文名称:L-氨基酸氧化酶
靶点别称
上市药物数量:0
临床药物数量:0
最高研发阶段:临床前

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抗体药
 
细胞治疗
 
基因治疗
 
诊断
 
疫苗
 
化药
 
蛋白及多肽药物
 
神经科学
 
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IL4I1 分子别名

L-amino-acid oxidase,Interleukin 4 induced protein 1, IL4I1

IL4I1 分子背景

Interleukin-4-induced-1 (IL4I1) is s a key immunoregulator and acts as a negative regulator of anti-tumor immunity. IL4I1 could activate the Aryl hydrocarbon receptor (AHR) via the generation of indole metabolites and kynurenic acid. AHR associates with reduced survival in glioma patients, promotes cancer cell motility, and suppresses.

IL4I1 前沿进展

Differential Effects of IL4I1 Protein on Lymphocytes From Healthy and Multiple Sclerosis Patients
Davis, Hu, Nanescu et al
Pharmacol Res Perspect (2025) 13 (2), e70062
Abstract: Multiple sclerosis (MS) is a chronic inflammatory disease characterized by immune-mediated demyelination of the central nervous system, resulting in extensive neurological deficit and remyelination impairment. We have previously found that interleukin-four induced one (IL4I1) protein modulates CNS inflammation and enhances remyelination in mouse models of experimental demyelination. However, it remained unclear if IL4I1 regulates lymphocyte activity in MS. To assess the therapeutic potential of IL4I1 in MS, we investigated the impact of IL4I1 treatment on human lymphocytes from peripheral blood mononuclear cells (PBMCs) obtained from healthy individuals and MS patients. We found that IL4I1 increased the relative densities of Th2 and regulatory T-cells, while reducing Th17 cell density in healthy control (HC) samples. Furthermore, IL4I1-treated lymphocytes promoted CNS remyelination when grafted into demyelinated spinal cord lesions in mice. We found that baseline endogenous IL4I1 expression was reduced in people with MS. However, unlike HCs, IL4I1 treatment had no significant effect on IL17 or TOB1 expression in lymphocytes derived from MS patients. These results suggest that IL4I1 skews CD4+ T-cells to a regulatory state in healthy human lymphocytes, which may be essential for promoting remyelination. However, IL4I1 appears unable to exert its influence on lymphocytes in MS, indicating that impaired IL4I1-mediated activity may underlie MS pathology.© 2025 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.
Monocyte-lineage tumor infiltration predicts immunoradiotherapy response in advanced pretreated soft-tissue sarcoma: phase 2 trial results
Levy, Morel, Texier et al
Signal Transduct Target Ther (2025) 10 (1), 103
Abstract: Immunoradiotherapy holds promise for improving outcomes in patients with advanced solid tumors, including in soft-tissue sarcoma (STS). However, the ideal combination of treatment modalities remains to be determined, and reliable biomarkers to predict which patients will benefit are lacking. Here, we report the results of the STS cohort of the SABR-PDL1 phase II trial that evaluated the anti-PDL1 atezolizumab combined with stereotactic body radiation therapy (SBRT) delivered concurrently with the 2nd cycle to at least one tumor site. Eligible patients received atezolizumab until progression or unmanageable toxicity, with SBRT at 45 Gy in 3 fractions). The primary endpoint was one-year progression-free survival (PFS) rate with success defined as 13 patients achieving 1-year PFS. Sixty-one heavily pretreated patients with STS (median 5 prior lines; 52% men; median age 54 years; 28% leiomyosarcoma) were enrolled across two centers (France, Spain). SBRT was delivered to 55 patients (90%), with the lung being the most commonly irradiated site (50%). After a median follow-up of 45 months, the one-year PFS rate was 8.3% [95% CI: 3.6-18.1]. Median PFS and overall survival were 2.5 and 8.6 months, respectively. Best responses included partial responses (5%) and stable disease (60%). Immune profiling revealed increased immunosuppressive tumor-associated macrophages (e.g., IL4I1, HES1) and monocyte-recruiting chemokines in non-responders. Higher monocyte/lymphocyte ratios (MonoLR) in tumor and blood correlated with progression. PD-L1 status, lymphoid infiltration, and tertiary-lymphoid structures were not predictive. Although the primary endpoint was not met, this study highlights MonoLR imbalance as a potential biomarker to identify STS patients likely to benefit from immunoradiotherapy. EudraCT No. 2015-005464-42; Clinicaltrial.gov number: NCT02992912.© 2025. The Author(s).
Spatial Metabolomics and Transcriptomics Reveal Metabolic Reprogramming and Cellular Interactions in Nasopharyngeal Carcinoma with High PD-1 Expression and Therapeutic Response
Ji, Wang, Zhuo et al
Theranostics (2025) 15 (7), 3035-3054
Abstract: Nasopharyngeal carcinoma (NPC) is a heterogeneous cancer with variable therapeutic responses, highlighting the need to better understand the molecular factors influencing treatment outcomes. This study aims to explore spatially metabolic and gene expression alterations in NPC patients with different therapeutic responses and PD-1 expression levels. Methods: This study employs spatial metabolomics (SM) and spatial transcriptomics (ST) to investigate significant alterations in metabolic pathways and metabolites in NPC patients exhibiting therapeutic sensitivity or elevated programmed death 1 (PD-1) expression. The spatial distribution of various cell types within the TME and their complex interactions were also investigated. Identified prognostic targets were validated using public datasets from TCGA, and further substantiated by in vitro functional analyses. Results: SM analysis revealed substantial reprogramming in lipid metabolism, branched-chain amino acid (BCAA) metabolism, and glutamine metabolism, which were closely associated with therapeutic response and PD-1 expression. ST analysis highlighted the critical role of interactions between precursor T cells and malignant epithelial cells in modulating therapeutic response in NPC. Notably, six key genes involved in BCAA metabolism (IL4I1, OXCT1, BCAT2, DLD, ALDH1B1, HADH) were identified in distinguishing patients with therapeutic sensitivity from those with therapeutic resistance. Functional validation of DLD and IL4I1 revealed that gene silencing significantly inhibited NPC cell proliferation, colony formation, wound healing, and invasion. Silencing DLD or IL4I1 induced cell cycle arrest. Reduction in α-Ketomethylvaleric acid (KMV) levels was demonstrated upon IL4I1 silencing. Immunohistochemical analysis further confirmed that high expression of these six genes was significantly associated with poor prognosis in NPC patients, a trend corroborated by data from the TCGA head and neck cancer cohort. Conclusions: This study highlights the pivotal roles of key molecular players in therapeutic response in NPC, providing compelling evidence for their potential application as prognostic biomarkers and therapeutic targets, thereby contributing to precision oncology strategies aimed at improving patient outcomes.© The author(s).
Showing 1-3 of 166 papers.
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