呼吸道病毒感染可重编肺巨噬细胞的抗感染功能，但病毒训练的巨噬细胞在肺部抗肿瘤免疫中的潜在功能尚未被充分了解，而肺部是原发性和转移性恶性肿瘤的优先靶点。我们在小鼠流感和肺部转移性肿瘤模型中发现，流感训练呼吸道黏膜居民肺泡巨噬细胞（AMs），让它们具备持久而组织特异性的抗肿瘤免疫力。经过训练的肺泡巨噬细胞渗透到肿瘤病灶中并具有增强的吞噬和肿瘤细胞细胞毒作用，这与表观遗传、转录和代谢抗瘤免疫抑制有关。AMs的抗肿瘤训练免疫的产生取决于干扰素-γ和自然杀伤细胞。值得注意的是，在非小细胞肺癌组织中具有训练免疫特征的人类AMs与良好的免疫微环境相关联。这些数据揭示了肺部粘膜居民巨噬细胞在抗肿瘤免疫监测中的作用，对组织-居留巨噬细胞进行训练免疫可能是潜在的抗肿瘤策略。 ©2023年作者等，独家许可Springer Nature America，Inc.

Respiratory viral infections reprogram pulmonary macrophages with altered anti-infectious functions. However, the potential function of virus-trained macrophages in antitumor immunity in the lung, a preferential target of both primary and metastatic malignancies, is not well understood. Using mouse models of influenza and lung metastatic tumors, we show here that influenza trains respiratory mucosal-resident alveolar macrophages (AMs) to exert long-lasting and tissue-specific antitumor immunity. Trained AMs infiltrate tumor lesions and have enhanced phagocytic and tumor cell cytotoxic functions, which are associated with epigenetic, transcriptional and metabolic resistance to tumor-induced immune suppression. Generation of antitumor trained immunity in AMs is dependent on interferon-γ and natural killer cells. Notably, human AMs with trained immunity traits in non-small cell lung cancer tissue are associated with a favorable immune microenvironment. These data reveal a function for trained resident macrophages in pulmonary mucosal antitumor immune surveillance. Induction of trained immunity in tissue-resident macrophages might thereby be a potential antitumor strategy.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.