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Harnessing skin-resident γδ T cells for immunotherapy in cutaneous squamous cell carcinoma
Giorgia Nasi1, Leonie C Schöftner1,2, Lara Ronacher1
1Department of Biosciences and Medical Biology, University of Salzburg, Salzburg, Austria.
Abstract:
Gamma delta (γδ) T cells are critical for tissue immune surveillance and their presence in tumors correlates with a favorable prognosis, highlighting their therapeutic potential. Although γδ T cells are abundant in the skin, their therapeutic value in skin cancer has remained largely unexplored due to challenges in isolating sufficient numbers of γδ T cells from human tissues and a lack of suitable preclinical models for skin cancer. Here, we are using innovative methods to expand human cutaneous γδ T cells ex vivo, enabling us to investigate their therapeutic potential in a human cutaneous squamous cell carcinoma (cSCC) mouse model. In this model, γδ T cells were specifically recruited to and maintained in the cSCC xenograft. These tumor-infiltrating cells exhibited an activated, cytotoxic phenotype and demonstrated effective antitumor activity in vivo. Collectively, our findings provide preclinical evidence supporting human skin-resident γδ T cells as a promising immunotherapeutic approach for treating skin cancers such as cSCC.
Insights
Gamma delta (γδ) T cells show promise for treating skin cancer. Researchers expanded these immune cells ex vivo and found they effectively targeted and reduced tumors in a preclinical skin cancer model.
Area of Science:
- Immunology
- Oncology
- Dermatology
Background:
- Gamma delta (γδ) T cells are vital for immune surveillance and are linked to better tumor prognoses.
- Their therapeutic potential in skin cancer is understudied due to isolation difficulties and lack of models.
Purpose of the Study:
- To investigate the therapeutic potential of ex vivo expanded human cutaneous γδ T cells in a skin cancer model.
- To establish a preclinical model for studying γδ T cell-based immunotherapy in cutaneous squamous cell carcinoma (cSCC).
Main Methods:
- Innovative ex vivo expansion techniques were used to generate sufficient numbers of human cutaneous γδ T cells.
- A human cSCC xenograft mouse model was utilized to assess γδ T cell recruitment, phenotype, and antitumor activity.
Main Results:
- Expanded γδ T cells were effectively recruited to and persisted within the cSCC xenografts.
- Tumor-infiltrating γδ T cells displayed an activated, cytotoxic phenotype.
- These cells demonstrated significant in vivo antitumor activity against cSCC.
Conclusions:
- Preclinical data support the use of human skin-resident γδ T cells as a viable immunotherapeutic strategy for skin cancers like cSCC.
- This study provides a foundation for developing γδ T cell-based therapies for skin malignancies.
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