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.