Harnessing skin-resident γδ T cells for immunotherapy in cutaneous squamous cell carcinoma
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.
Authors
- Christina Guttmann‐Gruber (ORCID: https://orcid.org/0000-0001-8232-5068)
- Oliver Nussbaumer (ORCID: https://orcid.org/0000-0002-4017-0990)
- Teresa Burner
- Martin Laimer (ORCID: https://orcid.org/0000-0002-6932-0374)
- Iris K. Gratz (ORCID: https://orcid.org/0000-0001-7470-7277)
- Roland Zauner (ORCID: https://orcid.org/0000-0003-0590-3877)
- Giorgia Nasi
- Monika Ettinger
- Suraj R. Varkhande (ORCID: https://orcid.org/0000-0001-8813-0907)
- Anshu Sharma (ORCID: https://orcid.org/0000-0002-2003-2945)
- Teodora Aleksandrova (ORCID: https://orcid.org/0000-0002-9940-961X)
- Andrew Hutton
- Lara Ronacher
- Amalia Sophianidis (ORCID: https://orcid.org/0009-0007-0818-0922)
- Johanna Moser-Waxenecker (ORCID: https://orcid.org/0009-0008-7401-1171)
- Leonie C. Schöftner (ORCID: https://orcid.org/0009-0007-7693-6568)
- Julia Feiser (ORCID: https://orcid.org/0009-0005-6615-3506)
Institutions
- Johannes Kepler University of Linz (AT)
- University of Salzburg (AT)
- Paracelsus Medical University (AT)
- Kepler Universitätsklinikum (AT)
- Unfallkrankenhaus Salzburg (AT)
- EB House Austria (AT)
- Benaroya Research Institute
- Takeda (Japan) (JP)
Publication Details
- Journal
- Science Advances
- Published
- 2026-06-24
- DOI
- https://doi.org/10.1126/sciadv.aec7215
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Francis Crick Institute
- King's College London
- Austrian Science Fund
- Universität Salzburg
- Paracelsus Medizinische Privatuniversität