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

Our plain-English summary of The Immunomodulatory Activity of Thymosin Alpha 1 on Tumor Cell Lines and Distinct Immune Cell Subsets, by L. Solmonese, M.F. Lofiego, C. Fazio, et al (OncoTargets and Therapy, 2025).

The study

• Authors: L. Solmonese, M.F. Lofiego, C. Fazio, F. Marzani, F. Piazzini, E. Bello, F. Celesti, G. Giacobini, X. Wang, M. Maio, S. Coral, A.M. Di Giacomo, A. Covre
• Journal: OncoTargets and Therapy
• Published: 2025;18:995-1012
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

© 2025 Solmonese et al.

In plain English

This laboratory study tested whether thymosin alpha 1 (Tα1), a thymic peptide drug, changes the immune-related gene activity of cancer cells and the behavior of immune cells. The authors treated 13 tumor cell lines (cutaneous melanoma, glioblastoma and pleural mesothelioma) and immune cells from 3 healthy donors with Tα1 for 48 hours. Tα1 did not slow tumor cell growth. In the pleural mesothelioma cell lines, a mean of 136 of 770 genes changed activity, but Tα1 showed very limited ability to alter immune-related genes in any tumor type. Only one gene was commonly raised (MMP-9) and one commonly lowered (TBX21) across all three tumor types. In immune cells, Tα1 increased growth of activated CD4+ T, B and NK cells, and its largest effect on gene activity was in CD8+ T cells. It did not significantly change the killing activity of LAK cells or cytotoxic T cells. The authors concluded that Tα1 was ineffective in changing the immune profile of tumor cells but directly stimulated immune cells. They called the work preliminary and asked for larger studies in cancer patients.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: in vitro laboratory study of tumor cell lines and immune cells
• Who was studied: 13 tumor cell lines from 3 tumor types: cutaneous melanoma, glioblastoma, and pleural mesothelioma (Meso4, Meso6 and Meso7). Also CD4+ T, CD8+ T, B and NK cell subsets from 3 healthy donors.
• Exposure: Laboratory treatment with thymosin alpha 1 (Tα1) for 48 hours: 10 µM for tumor cell lines and 3 µM for immune cells. No asbestos or fiber exposure was studied.
• Main results:
  • Tumor cell lines: Tα1 at 1, 10 and 100 µM showed no anti-proliferative or cytotoxic effect, with proliferation above 80% in every tested cell line.
  • Pleural mesothelioma cell lines: a mean of 136 genes (range 125 to 147) of 770 were differentially expressed after Tα1 treatment. The figures were 142 for melanoma and 163 for glioblastoma.
  • In the tumor cell lines of each type, Tα1 showed very limited ability to change the expression of immune-related genes.
  • Tumor cell lines: at the protein level, Tα1 did not change HLA class I, CD54, PD-L1 or MART-1.
  • Across all three tumor types, only one gene was commonly up-regulated (MMP-9) and one commonly down-regulated (TBX21).
  • Pleural mesothelioma cell lines: 6 of 11 significant biological processes from up-regulated genes were immune-related, as were 0 of 2 from down-regulated genes.
  • Healthy-donor immune cells: Tα1 at 3 µM gave statistically significant increases in proliferation of activated CD4+ T cells (140%), B cells (113%) and NK cells (179%).
  • Among the immune cell subsets, Tα1 had its greatest effect on CD8+ T cells, and the effect was stronger in activated than in resting cells.
  • Tα1 treatment did not significantly change the killing activity of LAK cells or of cytotoxic T cells against their target tumor cells.
• The authors' conclusion: The authors concluded that Tα1 was ineffective in modulating the immune profile of tumor cells, which led them to question its overall immunomodulatory potential on cancer. They also concluded that it had a direct stimulatory effect on distinct immune cell populations from healthy donors.
• Limitations the authors state:
  • The immune cell work used cells from a small number of healthy donors and was intended as preliminary work.
  • The authors said their findings need confirmation in a larger follow-up study in cancer patients' immune cells, using in vitro and in vivo tests.

Topics

Medical terms in this study, explained in our Lexicon: Immunotherapy, Pleural Mesothelioma, Tumor Microenvironment.

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