Related Experiment Video
Updated: Aug 11, 2025
Expansion and Enrichment of Gamma-Delta γδ T Cells from Apheresed Human Product
Published on: September 22, 2021
The antitumor activity of human Vγ9Vδ2 T cells is impaired by TGF-β through significant phenotype, transcriptomic and
Chirine Rafia1,2, Clément Loizeau1,2, Ophélie Renoult1,2
1Nantes Université, Inserm UMR 1307, CNRS UMR 6075, Université d'Angers, CRCI2NA, Nantes, France.
Abstract:
Despite significant advances, the eradication of cancer remains a clinical challenge which justifies the urgent exploration of additional therapeutic strategies such as immunotherapies. Human peripheral Vγ9Vδ2 T cells represent an attractive candidate subset for designing safe, feasible and effective adoptive T cell transfer-based therapies. However, following their infiltration within tumors, γδ T cells are exposed to various regulating constituents and signals from the tumor microenvironment (TME), which severely alter their antitumor functions. Here, we show that TGF-β, whose elevated production in some solid tumors is linked to a poor prognosis, interferes with the antigenic activation of human Vγ9Vδ2 T cells in vitro. This regulatory cytokine strongly impairs their cytolytic activity, which is accompanied by the induction of particular phenotypic, transcriptomic and metabolic changes. Collectively, these observations provide information for better understanding and targeting the impact of TME components to regulate the antitumor activity of human T cell effectors.
Insights
Transforming cancer therapy, this study reveals how tumor microenvironments suppress Vγ9Vδ2 T cell activity. Understanding these suppressive mechanisms, like TGF-β
Area of Science:
- Immunology
- Cancer Biology
- Cellular Therapy
Background:
- Cancer immunotherapy, particularly adoptive T cell transfer, shows promise but faces challenges.
- Human Vγ9Vδ2 T cells are a viable option for adoptive cell therapy.
- The tumor microenvironment (TME) can impair the anti-cancer functions of infiltrating T cells.
Purpose of the Study:
- To investigate the impact of the tumor microenvironment (TME) on human Vγ9Vδ2 T cell activity.
- To elucidate the role of transforming growth factor-beta (TGF-β) in modulating Vγ9Vδ2 T cell function within the TME.
- To understand the molecular and cellular mechanisms underlying TME-mediated suppression of Vγ9Vδ2 T cells.
Main Methods:
- In vitro co-culture systems to model TME interactions.
- Analysis of Vγ9Vδ2 T cell activation, cytolytic activity, phenotype, transcriptome, and metabolism.
- Quantification of TGF-β levels in relation to tumor progression.
Main Results:
- Elevated TGF-β in the TME significantly impairs the antigenic activation and cytolytic activity of human Vγ9Vδ2 T cells.
- TGF-β induces distinct phenotypic, transcriptomic, and metabolic alterations in Vγ9Vδ2 T cells.
- These changes collectively contribute to suppressed antitumor functions.
Conclusions:
- TGF-β is a key TME component that inhibits human Vγ9Vδ2 T cell-mediated anti-cancer immunity.
- Targeting TGF-β or its downstream effects may enhance the efficacy of Vγ9Vδ2 T cell-based immunotherapies.
- Further research into TME-effector cell interactions is crucial for optimizing cancer treatment strategies.
Related Concept Videos
01:27Tumor Immunotherapy
01:16TGF - β Signaling Pathway