Integrative cross‐tissue and spatially resolved single‐cell profiling uncovers tumour‐educated inflammatory remodelling of tissue‐resident macrophage ecosystem with immunotherapeutic prognostic significance in pan‐cancer.
Saved in:
| Title: | Integrative cross‐tissue and spatially resolved single‐cell profiling uncovers tumour‐educated inflammatory remodelling of tissue‐resident macrophage ecosystem with immunotherapeutic prognostic significance in pan‐cancer. |
|---|---|
| Authors: | Wang, Weikai, Chen, Zibin, Huang, Yuhan, Hu, Zhihao, Zhu, Peixin, Huang, Zhuoli, Lv, Jingzhi, Liao, Ziru, Zheng, Yuhui, Wei, Chen, Guan, Baibing, Zeng, Yin, Zhu, Xinyue, Yang, Yafei, Li, Guibo, Jin, Xin, Chen, Xi, Yang, Xiao, Ma, Zikun, Yin, Jianhua |
| Source: | Clinical & Translational Medicine; Feb2026, Vol. 16 Issue 2, p1-32, 32p |
| Subject Terms: | MACROPHAGES, TUMOR microenvironment, CELL analysis, RNA sequencing, IMMUNE checkpoint inhibitors, TUMORS, MACROPHAGE activation, MACROPHAGE inflammatory proteins |
| Abstract: | Background: Tissue‐resident macrophages (TRMs) exhibit dual roles in tumor progression, yet their functional reprogramming within the tumor microenvironment (TME) remains a critical unresolved question. Methods: We integrated single‐cell and spatial transcriptomics from a pan‐cancer atlas of 1.39 million cells across five malignancies with 2,318 bulk RNA‐seq samples to investigate macrophage states. A TRM inflammatory remodeling signature (TIR‐Sig) was developed for clinical biomarker validation. Results: We identified a conserved inflammatory TRM subtype (iTRM) characterized by CXCL8/IL1B/IL6 co‐expression that correlates with poor clinical outcomes. Crucially, both TRMs and monocyte‐derived tumor‐associated macrophages (Mono‐TAMs) underwent convergent differentiation into functionally similar inflammatory phenotypes, establishing iTRM as a universal tumor‐educated state. Further integration analysis revealed an iTRM‐enriched TME subtype which featured coordinated infiltration of neutrophils and cancer‐associated fibroblasts (CAFs), forming a 'cold tumor' ecosystem associated with immune checkpoint blockade (ICB) resistance and poor prognosis. The derived TRM inflammatory remodeling signature (TIR‐Sig) demonstrated dual clinical utility: it predicted patient survival (HR = 19.86, p <.001) and stratified ICB responders (AUC =.706). Conclusion: This study establishes phenotypic links between tissue‐resident and recruited macrophages through inflammatory reprogramming within TME, provides a unifying framework for pan‐cancer macrophage plasticity in TME, delivers a clinically actionable biomarker suite (TIR‐Sig), and provides potential therapeutic targets for TME remodeling. Key points: Cross‐tissue single‐cell atlas of tissue‐resident macrophages (TRMs).Identification of conserved inflammatory TRM phenotype (iTRM) in pan‐cancer.Dynamic convergence of TRM and monocyte‐derived macrophage lineages.TRM inflammatory remodelling signature (TIR‐Sig) with clinical potential. [ABSTRACT FROM AUTHOR] |
| Copyright of Clinical & Translational Medicine is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Biomedical Index |
Full Text 
Full Text Finder 
Nájsť tento článok vo Web of Science Be the first to leave a comment!