2026-02-24 中国科学院(CAS)
<関連情報>
- https://english.cas.cn/newsroom/cas-in-media/202602/t20260224_1151120.shtml
- https://www.cell.com/cell/abstract/S0092-8674(25)01491-6
CLIM-TIMEがT細胞療法への反応における転移性微小環境調節因子を特定 CLIM-TIME identifies metastatic microenvironment modulators for T cell therapy response
Yinghua Wang ∙ Weiwei Hu,, ∙ Rui Xia ∙ … ∙ Naihe Jing ∙ Luonan Chen, ∙ Guangchuan Wang
Cell Published:February 11, 2026
DOI:https://doi.org/10.1016/j.cell.2025.12.042
Graphical abstract
Highlights
- CLIM-TIME spatially maps the tumor microenvironment after tumor suppressor gene loss
- Seven metastatic TME subtypes are defined and associated with immune states
- Hippo-YAP loss shapes myeloid-rich T cell-excluded niches high in extracellular matrix
- LOXL2 inhibition remodels metastases, improving T cell infiltration and immunotherapy
Summary
The tumor microenvironment (TME) poses a major barrier to effective immunotherapy, yet high-throughput perturbation-mapping approaches to dissect TME spatial complexity and its contextual immune modulators remain lacking. Here, we introduce CRISPR-laser-captured microdissection (LCM) integration mapping of the tumor-immune microenvironment (CLIM-TIME), a scalable platform that integrates CRISPR screening with LCM of metastatic tumors for transcriptomic, deconvolution, and immunofluorescence analyses. CLIM-TIME enables spatially resolved mapping of how tumor suppressor gene (TSG) loss reshapes the TME and modulates immune responses. We identified seven distinct TME subtypes, revealing that DNA repair and Polycomb repressive complex (PRC) TSG loss is linked to immune-infiltrated TMEs sensitive to T cell therapy. In contrast, knockouts of TSGs in the Hippo pathway promoted immune evasion and therapy resistance by fostering myeloid-enriched but T cell-excluded TMEs with elevated extracellular matrix (ECM). Targeting the ECM-crosslinking enzyme LOXL2 effectively remodeled the metastatic TME, enhancing T cell infiltration and improving therapeutic efficacy in lung metastases across multiple cancers.
