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.

Science Advances
|June 24, 2026
PubMed

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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