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Influenza-trained mucosal-resident alveolar macrophages confer long-term antitumor immunity in the lungs [RNA-seq]

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE222149 | GEO | 2023/01/09

REPOSITORIES: GEO

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Influenza-trained mucosal-resident alveolar macrophages confer long-term antitumor immunity in the lungs [ATAC-seq]

Project description: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.

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Trained immunity of alveolar macrophages promotes injury resolution by enhancing KLF4-MERTK-mediated efferocytosis [RNA-seq]

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Influenza-trained mucosal-resident alveolar macrophages confer long-term antitumor immunity in the lungs

Project description:Influenza-trained mucosal-resident alveolar macrophages confer long-term antitumor immunity in the lungs

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SARS-CoV-2 Evades immune detection in Alveolar Macrophages

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Project description:Influenza-trained mucosal-resident alveolar macrophages confer long-term antitumor immunity in the lungs [RNA-seq]

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Trained immunity induction by the inactivated mucosal vaccine MV130 protects against experimental viral respiratory infections

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