{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE337nnn/GSE337933/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Mus musculus"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE337933"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"PTPN1/2 inhibits alveolar macrophage-mediated control of lung metastasis [CosMx SMI]","description":"Metastasis remains the leading cause of cancer mortality, yet effective therapies are limited. While therapeutic responses are influenced by organ-specific immune microenvironments, strategies to pharmacologically modulate these niches remain poorly defined. Here, using the clinical-stage inhibitor ABBV-CLS-484 (AC484) as a chemical probe, we demonstrate that systemic PTPN1/2 inhibition remodels the pulmonary myeloid landscape, specifically activating alveolar macrophages (AMs) toward a tumoricidal state. Integrated single-cell/spatial transcriptomics and functional assays reveal that AC484 promotes AM accumulation within metastatic lesions, elevates their IFNγ production and responsiveness, and enhances their tumor-killing activity. Depletion of AMs diminishes the anti-metastatic efficacy of AC484. Mechanistically, inhibiting PTPN1/2 by AC484 amplifies IFNγ-STAT1 signaling in AMs, while disrupting this pathway impairs their tumor control capability. These findings delineate a distinct innate immune axis where PTPN1/2 acts as a molecular \"brake\" on AM activation, suggesting that pharmacologically unleashing tissue-resident macrophages offers a therapeutic strategy to overcome metastatic progression, particularly in microenvironments where adaptive immunity is insufficient.","dates":{"publication":"2026/09/02"},"accession":"GSE337933","cross_references":{"GSM":["GSM9863174"],"GPL":["36279"],"GSE":["337933"],"taxon":["Mus musculus"]}}