恶性扩张和快速转移是限制肺癌成功治疗的主要因素。信使RNA（mRNA）肿瘤疫苗是一种有前景的肺癌免疫治疗方法，也适用于其他转移性肿瘤。在这里，我们开发了一种mPLA/mRNA肿瘤疫苗（mLPR），利用TLR4激动剂mPLA将mRNA转运到细胞质并改善免疫反应。经鼻给药后，mLPR疫苗能刺激树突状细胞的成熟，重新编程M2巨噬细胞为M1巨噬细胞，同时交叉激活先天和适应性免疫反应。mLPR疫苗通过免疫细胞的活化、IFN-γ/IL-12细胞因子的分泌和自然杀伤细胞介导的抗体依赖性细胞毒作用，抑制了肺癌的发展并减少了骨转移。mPLA/mRNA肿瘤疫苗将为肺癌治疗中的mRNA肿瘤疫苗的应用提供思路和应用前景。 SIGNIFICANCE声明：肺癌和骨转移严重影响患者的生存，传统的治疗方法效率低且有许多副作用。我们构建了一种同时激活机体先天免疫和适应性免疫的mRNA疫苗，以实现更好的免疫治疗效果。总之，通过疫苗设计和体外和体内免疫学研究，我们确认了mLPR疫苗刺激了树突状细胞的成熟，将M2巨噬细胞重新编程为M1巨噬细胞，同时在体内交叉激活了免疫反应和适应性免疫。版权所有ⓒ2023年。Elsevier Ltd.发表

Malignant expansion and rapid metastasis are the main limiting factors to successful treatment of lung cancer. Messenger RNA (mRNA) tumor vaccines are a promising immunotherapeutic treatment for lung cancer as well as other metastatic cancers. Herein, we developed a mPLA/mRNA tumor vaccine (mLPR) to escort mRNA into the cytoplasm and improve immune response with the help of TLR4 agonist mPLA. After nasal administration, the mLPR vaccine stimulated the maturation of dendritic cells, reprogramed M2 macrophages into M1 macrophages, as well cross-activated innate and adaptive immune responses. The mLPR vaccine inhibited the development of lung cancer and reduced bone metastasis by means of immune cell activation, IFN-γ/IL-12 cytokine secretion, and natural killer cell-mediated antibody dependent cellular cytotoxicity. The mPLA/mRNA tumor vaccine will provide ideas and application prospects for the use of mRNA tumor vaccine in the treatment of lung cancer. STATEMENT OF SIGNIFICANCE: : Lung cancer and bone metastasis seriously affect patient survival, and traditional treatment methods are inefficient and have many side effects. We have constructed an mRNA vaccine that simultaneously activates the innate immune and adaptive responses of the body, in order to achieve better immunotherapeutic effects. To sum up, we confirmed through vaccine design and in vitro and in vivo immunological studies that the mLPR vaccine stimulated the maturation of dendritic cells, reprogrammed M2 macrophages into M1 macrophages, as well cross activated in vivo and adaptive immune responses.Copyright © 2023. Published by Elsevier Ltd.