LAUSR

Cutaneous squamous cell carcinoma (CSCC), which develops in response to ultraviolet irradiation exposure, is among the most common cancers. CSCC lesions can be removed by surgical excision, but 4.5% of these cancers reappear as aggressive and therapy‐resistant tumors. CSCC tumors display a high mutation burden, and tumor frequency is dramatically increased in immune‐suppressed patients, indicating a vital role for the immune system in controlling cancer development. Natural killer cells (NK cells) play a key role in cancer immune surveillance, and recent studies suggest that NK cells from healthy donors can be expanded from peripheral blood for use in therapy. In the present study, we test the ability of ex vivo expanded human NK cells to suppress the CSCC cell cancer phenotype and reduce tumor growth. We expanded human NK cells from multiple healthy donors, in the presence of IL‐2, and tested their ability to suppress the CSCC cell cancer phenotype. NK cell treatment produced a dose‐dependent reduction in SCC‐13 and HaCaT cell spheroid growth and matrigel invasion and induced SCC‐13 and HaCaT cell apoptosis as evidenced by increased procaspase 9, procaspase 3, and PARP cleavage. Moreover, two important CSCC cell pro‐cancer signaling pathways, YAP1/TAZ/TEAD and MEK1/2‐ERK1/2, were markedly reduced. Furthermore, tail‐vein injection of NK cells markedly suppressed the growth of SCC‐13 xenograft tumors in NSG mice, which was also associated with a reduction in YAP1 and MEK1/2‐P levels and enhanced apoptosis. These findings show that NK cell treatment suppresses CSCC cell spheroid formation, invasion, viability, and tumor growth, suggesting NK cell treatment may be a candidate therapy for CSCC.