biostudies-literatureZhu CWu Jieping Medical FoundationNational Natural Science Foundation of China102671https://www.ebi.ac.uk/biostudies/studies/S-EPMC12903197biostudies-literatureUnknown65<h4>Background</h4>Lung adenocarcinoma (LUAD) remains a major clinical challenge in assessment of clinical outcomes and therapeutic response. Although tumor-associated macrophages (TAMs) are known as crucial regulators of tumor progression, their heterogeneity and prognostic relevance in LUAD have not been fully elucidated.<h4>Methods</h4>The heterogeneity of TAMs was detected by integration analyses of single-cell data and spatial transcriptome data. The CTSB⁺ TAM-related signature (CTRS) was developed by machine learning algorithms across four LUAD datasets. Multi-omics analysis and functional experiments were applied to uncover the potential role and mechanism of CTSB⁺ TAMs in LUAD.<h4>Results</h4>Single-cell analysis identified CTSB⁺ TAM as a crucial player in LUATranslational oncologyCTSB-positive tumor-associated macrophages shape prognosis and therapeutic response in lung adenocarcinoma.PMC12903197320.6750.2025-13-2682003235Ding XTian MZhang ZXue NLiang LMei DSun XZhu CfalseCTSB-positive tumor-associated macrophages shape prognosis and therapeutic response in lung adenocarcinoma.<h4>Background</h4>Lung adenocarcinoma (LUAD) remains a major clinical challenge in assessment of clinical outcomes and therapeutic response. Although tumor-associated macrophages (TAMs) are known as crucial regulators of tumor progression, their heterogeneity and prognostic relevance in LUAD have not been fully elucidated.<h4>Methods</h4>The heterogeneity of TAMs was detected by integration analyses of single-cell data and spatial transcriptome data. The CTSB⁺ TAM-related signature (CTRS) was developed by machine learning algorithms across four LUAD datasets. Multi-omics analysis and functional experiments were applied to uncover the potential role and mechanism of CTSB⁺ TAMs in LUAD.<h4>Results</h4>Single-cell analysis identified CTSB⁺ TAM as a crucial player in LUA2026-01-01T00:00:00Z2026 Mar2026-07-15T15:39:20.926Z2026-07-06T03:11:58.836ZS-EPMC129031974152049110.1016/j.tranon.2026.102671