The Immunomodulatory Activity of Thymosin Alpha 1 on Tumor Cell Lines and Distinct Immune Cell Subsets.

IF 2.8 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

OncoTargets and therapy Pub Date : 2025-09-10 eCollection Date: 2025-01-01 DOI:10.2147/OTT.S527785

Laura Solmonese, Maria Fortunata Lofiego, Carolina Fazio, Francesco Marzani, Francesca Piazzini, Emma Bello, Fabrizio Celesti, Gianluca Giacobini, Xiaohui Wang, Michele Maio, Sandra Coral, Anna Maria Di Giacomo, Alessia Covre

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Abstract

Background: The immune-balancing role of thymosin alpha 1 (Tα1) is well-recognized in contexts of immune dysregulation. Within the anti-tumor context, Tα1 demonstrated to act as an immune-enhancer, with potential roles in immunotherapy-based treatments. However, Tα1 immunomodulatory potential on tumor cells is poorly understood. Additionally, Tα1 pleiotropic effects on immune cells require in-depth investigations to unravel its specific impact on different immune cell populations. Thus, we first aimed to investigate whether Tα1 treatments influenced the transcriptional immune profile of various cancer cell lines. Alongside, CD4⁺ T, CD8⁺ T, B, and natural killer cells from healthy donors (HDs) were treated individually with Tα1, to assess its direct effects on each immune cell population.

Methods: Cutaneous melanoma, glioblastoma, and pleural mesothelioma cell lines and HD immune cell subsets were treated with Tα1 for 48 hours. Total RNA was subsequently isolated, and gene expression profiles were analyzed by the nCounter^® SPRINT Profiler. Genes with a log2ratio ≥0.58 and ≤-0.58 in Tα1-treated vs untreated cells were defined as differentially expressed (DEGs) and subsequently evaluated for the enrichment of Gene Ontology terms to identify biological processes potentially affected by Tα1 in tumor and immune cells.

Results: Tα1 minimally changed cancer cell DEGs and immune-related biological processes, suggesting a comprehensive lack of transcriptional immunomodulatory potential on the tumor counterpart. Conversely, Tα1 exhibited to directly affect the proliferation and/or transcription processes of each studied immune cell subset, with the greatest transcriptional impact observed for activated CD8⁺ T cells, crucial players in anti-tumor immunity.

Conclusion: Our findings question the tumor immunomodulatory properties of Tα1, simultaneously underscoring the importance of further investigating Tα1 influence on specific immune cell subsets in the periphery or within the tumor microenvironment of cancer patients. This would contribute to understand Tα1 potential in immunotherapy-based combination strategies, within the anti-tumor setting.

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胸腺素α 1对肿瘤细胞系和不同免疫细胞亚群的免疫调节活性。

背景：胸腺素α1 （Tα1）在免疫失调中的免疫平衡作用已得到充分认识。在抗肿瘤的背景下，Tα1被证明是一种免疫增强剂，在基于免疫疗法的治疗中具有潜在的作用。然而，Tα1对肿瘤细胞的免疫调节作用尚不清楚。此外，Tα1对免疫细胞的多效性作用需要深入研究，以揭示其对不同免疫细胞群的特异性影响。因此，我们首先旨在研究Tα1治疗是否影响各种癌细胞系的转录免疫谱。同时，分别用Tα1治疗来自健康供体（hd）的CD4+ T、CD8+ T、B和自然杀伤细胞，以评估其对每种免疫细胞群的直接影响。方法：用Tα1治疗皮肤黑色素瘤、胶质母细胞瘤、胸膜间皮瘤细胞系及HD免疫细胞亚群48小时。随后分离总RNA，并使用nCounter®SPRINT Profiler分析基因表达谱。在Tα1处理和未处理的细胞中，log2比值≥0.58和≤-0.58的基因被定义为差异表达（deg），随后评估基因本体术语的富集程度，以确定肿瘤和免疫细胞中可能受Tα1影响的生物过程。结果：Tα1对癌细胞DEGs和免疫相关生物学过程的影响微乎其微，表明其对肿瘤对应物缺乏转录免疫调节潜力。相反，Tα1可以直接影响所研究的每个免疫细胞亚群的增殖和/或转录过程，其中对活化的CD8+ T细胞的转录影响最大，CD8+ T细胞是抗肿瘤免疫的关键角色。结论：我们的研究结果质疑了Tα1的肿瘤免疫调节特性，同时强调了进一步研究Tα1对肿瘤患者外周或肿瘤微环境中特异性免疫细胞亚群的影响的重要性。这将有助于了解Tα1在基于免疫治疗的联合策略中的潜力，在抗肿瘤设置中。

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来源期刊

OncoTargets and therapy BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ONCOLOGY

CiteScore

9.70

自引率

0.00%

发文量

221

审稿时长

1 months

期刊介绍： OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer. The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype. Specific topics covered by the journal include: -Novel therapeutic targets and innovative agents -Novel therapeutic regimens for improved benefit and/or decreased side effects -Early stage clinical trials Further considerations when submitting to OncoTargets and Therapy: -Studies containing in vivo animal model data will be considered favorably. -Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines. -Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples. -Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Single nucleotide polymorphism (SNP) studies will not be considered.