恶性肿瘤相关死亡的主要原因是转移。尽管转移进展是由多种肿瘤内在机制驱动的，但人们越来越重视肿瘤微环境的肿瘤外因素特别是巨噬细胞的贡献，这与不良临床结果相关。巨噬细胞包括骨髓来源和组织驻留的种群。与骨髓来源的巨噬细胞相比，掌控组织驻留巨噬细胞（TRMs）的促转移活动的转录途径仍不清楚。肺泡巨噬细胞(AMs)是组织驻留种群，具有组织稳态和转移的关键作用。Wnt/β-catenin信号通路是癌症的标志，并被识别为感染中AMs的病理调节因素。我们检验了这个假设，即AMs中β-catenin的表达增强了实体肿瘤模型的转移。通过遗传β-catenin增益功能方法，我们证明：（a）AMs中增强的β-catenin增加了肺转移；（b）AMs的β-catenin活性驱动了一个失调的炎症程序，与Tnf表达强烈相关；（c）局部TNF-α阻断消除了这种转移结果。最后，β-catenin基因CTNNB1和TNF表达水平与肺癌患者的AMs呈正相关。总的来说，我们的发现揭示了AMs中的Wnt/β-catenin/TNF-α促转移轴，对于肿瘤对TNF-α抗肿瘤作用无效的潜在治疗意义。

The main cause of malignancy-related mortality is metastasis. Although metastatic progression is driven by diverse tumor-intrinsic mechanisms, there is a growing appreciation for the contribution of tumor-extrinsic elements of the tumor microenvironment, especially macrophages, which correlate with poor clinical outcomes. Macrophages consist of bone marrow-derived and tissue-resident populations. In contrast to bone marrow-derived macrophages, the transcriptional pathways that govern the pro-metastatic activities of tissue-resident macrophages (TRMs) remain less clear. Alveolar macrophages (AMs) are a TRM population with critical roles in tissue homeostasis and metastasis. Wnt/β-catenin signaling is a hallmark of cancer and has been identified as a pathologic regulator of AMs in infection. We tested the hypothesis that β-catenin expression in AMs enhances metastasis in solid tumor models. Using a genetic β-catenin gain-of-function approach, we demonstrated that (a) enhanced β-catenin in AMs heightened lung metastasis; (b) β-catenin activity in AMs drove a dysregulated inflammatory program strongly associated with Tnf expression; and (c) localized TNF-α blockade abrogated this metastatic outcome. Last, β-catenin gene CTNNB1 and TNF expression levels were positively correlated in AMs of patients with lung cancer. Overall, our findings revealed a Wnt/β-catenin/TNF-α pro-metastatic axis in AMs with potential therapeutic implications against tumors refractory to the antineoplastic actions of TNF-α.