γδT细胞免疫疗法治疗肺癌的有效性和机制尚不清楚。在这项研究中，我们评估了持续、低剂量 γδT 细胞干预对肺癌细胞的影响。我们将 γδT 细胞与肺癌细胞系 (A549) 一起培养，并每 48 小时更换一次 γδT 细胞群。采用缩胆囊素八肽（CCK-8）法检测γδT细胞对A549细胞的杀伤作用及半数抑制浓度（IC50）值。通过 ELISA 测定共培养细胞上清液中穿孔素、颗粒酶 B 以及炎症因子白细胞介素 6 (IL-6)、干扰素 (IFN)-γ 和肿瘤坏死因子-α (TNF-a) 的水平。 Western blotting检测Bcl-2、Bax、PI3K、Akt蛋白表达。我们的结果表明，γδT 细胞处理降低了 Bcl-2、PI3K 和 AKT 的蛋白表达，但上调了 Bax 的蛋白表达。此外，γδT 细胞处理增加了与 Bax/Bcl-2 信号通路相关的穿孔素和颗粒酶 B 的释放。此外，γδT 细胞介导的 A549 细胞细胞溶解作用涉及 PI3K/AKT 途径。体内结果与体外结果一致。 γδT细胞免疫疗法对信号通路网络进行整合调节，涉及细胞凋亡和增殖的相互调节。 γδT 细胞免疫疗法可用于增强对肺癌细胞的细胞毒性杀伤。© 2023。作者，获得 Springer Nature Limited 的独家许可。

The effectiveness and mechanisms of γδT-cell immunotherapy in lung cancer remain unclear. In this study, we assessed the effects of continuous, low-dose γδT-cell intervention on lung cancer cells. We cultured γδT cells with a lung cancer cell line (A549) and replaced the γδT-cell population every 48 hours. The killing effect of γδTcells on A549 cells and the Half-maximal inhibitory concentration (IC50) value were detected by the cholecystokinin octapeptide (CCK-8) method. The levels of perforin, granzyme B and the inflammatory factors interleukin-6 (IL-6), interferon (IFN)-γ, and tumor necrosis factor-alpha (TNF-a), in the supernatants of cocultured cells were measured by ELISA. The protein expression of Bcl-2, Bax, PI3K and Akt was detected by western blotting. Our results indicated that γδT-cell treatment decreased the protein expression of Bcl-2, PI3K, and AKT but upregulated that of Bax. Moreover, γδT-cell treatment increased perforin and granzyme B release related to the Bax/Bcl-2 signaling pathway. In addition, γδT-cell-mediated cytolysis for A549 cells involved the PI3K/AKT pathway. In vivo results were consistent with the in vitro results. γδT-cell immunotherapy integrated regulation of a signaling pathway network involving the mutual regulation of apoptosis and proliferation. γδT-cell immunotherapy could be used to enhance the cytotoxic killing of lung cancer cells.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.