A Preliminary Study on the Therapeutic Role of γδT Cells in Triple-Negative Breast Cancer.

Abstract

This study was aimed to elucidate the cytotoxic effects of γδT cells on triple-negative breast cancer (TNBC) cells and assess their antitumor efficacy in a mouse xenograft model. Furthermore, the underlying mechanisms of γδT cell action on TNBC were explored. The study utilized three TNBC cell lines (MDA-MB-231, MDA-MB-468, and BT-549) as target cells, with γδT cells serving as effector cells. Cytotoxicity was assessed in different effector-to-target ratios (E:T) at 5:1, 10:1, and 20:1 subsequent to coculture. To evaluate the antitumor effects of γδT cells in vivo, a xenograft mice model was established by inoculating MDA-MB-231 cells into the mammary fat pad of B-NDG mice. The mice received tail vein injections of γδT cells at different doses. The effects on tumor growth, mouse body weight, and γδT cell accumulation in the spleen were then determined. γδΤ cells at E:T of 10:1 exhibited significant cytotoxicity against all three TNBC cell lines, indicating a statistically significant difference compared to the control group (p < 0.0001). The cytotoxic effect at this ratio was superior to that at 20:1 and 5:1 effector-to-target ratios, as evidenced by statistical significance (p < 0.05). Following 21 days of adoptive transfer via tail vein injection, γδΤ cells at both low and high doses significantly reduced tumor volume and mass compared to the PBS control group (p < 0.001). This reduction was accompanied by an increased accumulation of γδΤ cells in the spleen. In conclusion, γδΤ cells exert significant cytotoxic effects on TNBC cells and effectively inhibit the growth of breast cancer xenografts in mice while also promoting the accumulation of γδΤ cells in the mouse spleen.