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γδT细胞在三阴性乳腺癌治疗作用中的初步研究

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

作者信息

Qiu Shi, Han Qin-Yu, Zhao Xian, Li Wen-Jing, Li Xiang-Qi

机构信息

Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.

Department of Breast Center, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, Shandong, China.

出版信息

Kaohsiung J Med Sci. 2025 Aug;41(8):e70029. doi: 10.1002/kjm2.70029. Epub 2025 Apr 28.

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.

摘要

本研究旨在阐明γδT细胞对三阴性乳腺癌(TNBC)细胞的细胞毒性作用,并在小鼠异种移植模型中评估其抗肿瘤疗效。此外,还探讨了γδT细胞作用于TNBC的潜在机制。该研究使用三种TNBC细胞系(MDA-MB-231、MDA-MB-468和BT-549)作为靶细胞,γδT细胞作为效应细胞。共培养后,以5:1、10:1和20:1的不同效应细胞与靶细胞比例(E:T)评估细胞毒性。为了评估γδT细胞在体内的抗肿瘤作用,通过将MDA-MB-231细胞接种到B-NDG小鼠的乳腺脂肪垫中建立了异种移植小鼠模型。小鼠接受不同剂量的γδT细胞尾静脉注射。然后测定对肿瘤生长、小鼠体重和脾脏中γδT细胞积累的影响。E:T为10:1的γδT细胞对所有三种TNBC细胞系均表现出显著的细胞毒性,与对照组相比具有统计学显著差异(p < 0.0001)。该比例下的细胞毒性作用优于20:1和5:1效应细胞与靶细胞比例下的作用,具有统计学显著性(p < 0.05)。通过尾静脉注射进行过继转移21天后,与PBS对照组相比,低剂量和高剂量的γδT细胞均显著降低了肿瘤体积和质量(p < 0.001)。这种降低伴随着脾脏中γδT细胞积累的增加。总之,γδT细胞对TNBC细胞发挥显著的细胞毒性作用,有效抑制小鼠乳腺癌异种移植瘤的生长,同时还促进γδT细胞在小鼠脾脏中的积累。

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