在之前的研究中，我们开发了一种名为“melittin-MIL-2”的新型融合蛋白，它表现出更强的抗肿瘤活性。然而，melittin-MIL-2是否对肺腺癌具有抗肿瘤免疫作用尚不清楚。本研究将探讨melittin-MIL-2抑制肺腺癌生长和侵袭的免疫效应及机制，以期为肺癌的免疫治疗提供新的视角。结果表明，melittin-MIL-2 促进 T 细胞增殖，增强 NK 细胞的细胞毒性，并促进 PBMC 中 IFN-γ 的分泌。经过蜂毒肽-MIL-2刺激后，人PBMC和NK细胞的穿孔素表达和LAK/NK样杀伤活性显着增强。 Melittin-MIL-2能够阻碍肺腺癌细胞A549的发育和增殖。暴露于蜂毒素-MIL-2 的 A549 细胞中 ICAM-1 和 Fas 表达显着升高。 Melittin-MIL-2刺激后A549细胞中TLR8和VEGF的表达水平显着降低。在体内，蜂毒肽-MIL-2 显着阻碍了肺腺癌的生长，并在肿瘤组织中局部形成了免疫刺激微环境。总之，新型融合蛋白melittin-MIL-2通过激活LFA-1/ICAM-1和Fas/FasL通路增强细胞溶解活性，上调IFN-γ的分泌，在肺腺癌细胞A549中表现出强大的抗肿瘤免疫作用。 γ 和穿孔素，并增强 LAK/NK 样杀伤活性。免疫效应细胞及其分泌的细胞因子可以在肺腺癌Lewis小鼠组织中形成局部免疫刺激微环境。© 2024 作者。约翰·威利出版的《临床呼吸杂志》

In previous studies, we developed a novel fusion protein named "melittin-MIL-2" which exhibited more anti-tumor activity. However, it remains unclear whether melittin-MIL-2 possesses antitumor immune effect on lung adenocarcinoma. In this study, the immune effect and mechanism of melittin-MIL-2 inhibiting the growth and invasion of lung adenocarcinoma will be investigated, in order to provide novel perspectives for the immunotherapy of lung cancer. The results indicated that melittin-MIL-2 promoted T cell proliferation, enhanced NK cell cytotoxicity, and boosted IFN-γ secretion in PBMCs. After melittin-MIL-2 stimulation, perforin expression and LAK/NK-like killing activities of human PBMCs and NK cells were significantly enhanced. Melittin-MIL-2 is capable of hampering the development and proliferation of lung adenocarcinoma cell A549. ICAM-1 and Fas expression in A549 cells exposed to melittin-MIL-2 rose significantly. The expression levels of TLR8 and VEGF in A549 cells decreased significantly after melittin-MIL-2 stimulation. In vivo, melittin-MIL-2 substantially impeded the growth of lung adenocarcinoma and formed an immune-stimulating microenvironment locally in tumor tissues. In conclusion, the novel fusion protein melittin-MIL-2 exhibits strong anti-tumor immune effect in lung adenocarcinoma cell A549 via activating the LFA-1/ICAM-1 and Fas/FasL pathways to enhance cytolytic activity, upregulating the secretion of IFN-γ and perforin, and boosting LAK/NK-like killing activities. Immuno-effector cells and their secreted cytokines can form immune stimulation microenvironment locally in lung adenocarcinoma Lewis mice tissue.© 2024 The Author(s). The Clinical Respiratory Journal published by John Wiley & Sons Ltd.