ArticleThe Journal of clinical investigation2026
Macrophage-rich niches regulate T cell dynamics at the liver invasive margin during gallbladder cancer progression.
Article in The Journal of clinical investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Targeting macrophage-driven NK cell immunosuppression to improve cancer immunotherapy.Journal for immunotherapy of cancer · 2026Review
- New progress and clinical research translation of immune checkpoint inhibitors in systemic therapy of gallbladder cancer.Frontiers in immunology · 2026Review
- Spatial, single-nucleus and pathological profiling of the invasive front in early hepatocellular carcinoma for characterizing specific leading-edge cell niche and improving recurrence modeling.International journal of biological sciences · 2026Article
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Authors and funding
34 authors.
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Abstract
Liver invasion is one of the most frequent events in the progression of gallbladder cancer (GBC). However, the cellular and pathological role of the tumor-liver-interface microenvironment in liver invasion is still enigmatic. Here, we applied single-cell and spatial transcriptomics to systematically investigate the cellular component and gene expression regulation of the microenvironment from the tumor to the liver, specifically the invasive boundary. Our analyses revealed that CXCL9+ macrophage-rich immune cell niches were accumulated in the tumor-liver invasive margin, where 2 subclasses of the CXCL9+ immune cell niches, CXCL9+TRAC+ (CT) and CXCL9+C1QB+ (CC) niches, were identified. CD8+ T cells were recruited by CXCL9+ macrophages through CXCL9-CXCR3 interaction in the CT niche, which was located adjacent to the liver. Moreover, the CC niche was proximal to the tumor core, where tumor cells induced CD8+ T cell exhaustion via LGALS4 expression. In addition, our cohort study showed that high CXCL9 and low LGALS4 in the liver invasion margin demonstrated a favorable prognosis and better responses to anti-PD-1 immunotherapy for patients with gallbladder cancer. Altogether, these findings demonstrate novel cellular and molecular mechanisms underlying liver invasion and offer clinical value for immunotherapies.
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