Alveolar macrophages in lung cancer: opportunities challenges.
Alveolar macrophages in lung cancer: opportunities challenges.
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DOI：
10.3389/fimmu.2023.1268939
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发表时间：
2023
影响因子：
7.3
通讯作者：
Kheradmand, Farrah
中科院分区：
文献类型：
--
作者：
Chang, Cheng-Yen;Armstrong, Dominique;Corry, David B.;Kheradmand, Farrah
关键词：
肺泡巨噬细胞（AM）是肺先天防御机制的关键组成部分。来源于卵黄囊或骨髓的AM紧紧地依偎在肺泡内，可以吞噬外来颗粒，保护宿主免受病原体的侵害，回收表面活性剂，并迅速对吸入的有害刺激作出反应。AM的行为密切依赖于环境因素，感染、慢性炎症和相关的代谢变化可以恢复其在肺中的效应功能。肿瘤微环境中的几个因素可以重新教育AM，导致肿瘤生长，并降低非小细胞肺癌（NSCLC）患者的免疫检查点抑制剂（ICI）疗效。AM的可塑性及其在改变肿瘤对ICI的反应中的关键功能使其成为肺癌治疗的理想靶点。已经开发了新的策略来靶向实体瘤中的AM，重新编程其抑制功能并提高ICI的功效。在这里，我们审查的表型和功能的变化，在AM无菌炎症反应和非小细胞肺癌，可能是关键的肿瘤生长和转移。改变AM功能的机会包括利用它们在训练免疫中的潜在功能，这是一个从对感染的记忆反应中借用的概念，可以在治疗肺癌治疗中进行探索。
Alveolar macrophages (AMs) are critical components of the innate defense mechanism in the lung. Nestled tightly within the alveoli, AMs, derived from the yolk-sac or bone marrow, can phagocytose foreign particles, defend the host against pathogens, recycle surfactant, and promptly respond to inhaled noxious stimuli. The behavior of AMs is tightly dependent on the environmental cues whereby infection, chronic inflammation, and associated metabolic changes can repolarize their effector functions in the lungs. Several factors within the tumor microenvironment can re-educate AMs, resulting in tumor growth, and reducing immune checkpoint inhibitors (ICIs) efficacy in patients treated for non-small cell lung cancer (NSCLC). The plasticity of AMs and their critical function in altering tumor responses to ICIs make them a desirable target in lung cancer treatment. New strategies have been developed to target AMs in solid tumors reprograming their suppressive function and boosting the efficacy of ICIs. Here, we review the phenotypic and functional changes in AMs in response to sterile inflammation and in NSCLC that could be critical in tumor growth and metastasis. Opportunities in altering AMs’ function include harnessing their potential function in trained immunity, a concept borrowed from memory response to infections, which could be explored therapeutically in managing lung cancer treatment.
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