Work

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

Year: 2025

Type: article

Abstract: Background: The immune-balancing role of thymosin alpha 1 (Tα 1) is well-recognized in contexts of immune dysregulation. Within the anti-tumor context, Tα 1 demonstrated to act as an immune-enhancer, with potential roles in immunotherapy-based treatments. However, Tα 1 immunomodulatory potential on tumor cells is poorly understood. Additionally, Tα 1 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 Tα 1 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 Tα 1, 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 Tα 1 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 Tα 1-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 Tα 1 in tumor and immune cells. Results: Tα 1 minimally changed cancer cell DEGs and immune-related biological processes, suggesting a comprehensive lack of transcriptional immunomodulatory potential on the tumor counterpart. Conversely, Tα 1 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 Tα 1, simultaneously underscoring the importance of further investigating Tα 1 influence on specific immune cell subsets in the periphery or within the tumor microenvironment of cancer patients. This would contribute to understand Tα 1 potential in immunotherapy-based combination strategies, within the anti-tumor setting. Keywords: cancer, immune response, immunomodulatory agents, cancer immunotherapy

Source: OncoTargets and Therapy

DOI: 10.2147/ott.s527785