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
{"title":"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。","authors":"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","doi":"10.2147/OTT.S527785","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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<sup>+</sup> T, CD8<sup>+</sup> 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.</p><p><strong>Methods: </strong>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<sup>®</sup> 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.</p><p><strong>Results: </strong>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<sup>+</sup> T cells, crucial players in anti-tumor immunity.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"995-1012"},"PeriodicalIF":2.8000,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433645/pdf/","citationCount":"0","resultStr":"{\"title\":\"The Immunomodulatory Activity of Thymosin Alpha 1 on Tumor Cell Lines and Distinct Immune Cell Subsets.\",\"authors\":\"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\",\"doi\":\"10.2147/OTT.S527785\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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<sup>+</sup> T, CD8<sup>+</sup> 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.</p><p><strong>Methods: </strong>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<sup>®</sup> 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.</p><p><strong>Results: </strong>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<sup>+</sup> T cells, crucial players in anti-tumor immunity.</p><p><strong>Conclusion: </strong>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. 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The Immunomodulatory Activity of Thymosin Alpha 1 on Tumor Cell Lines and Distinct Immune Cell Subsets.
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.
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.