ArticleThe Journal of clinical investigation2025
Cxcr3 promotes protection from colorectal cancer liver metastasis by driving NK cell infiltration and plasticity.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- From Gut Microbiota to Hepatic Pre-Metastatic Niches: Mechanism and Translational Prospects of the Gut-Liver Axis in Regulating Colorectal Cancer Liver Metastasis.Microorganisms · 2026Review
- Nitric Oxide Conjugation Transforms NIR-II AIEgens Into Potent Hypoxia-Tolerant Type I Photosensitizers.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- IL-27 shapes NK cell heterogeneity and function in colorectal cancer.Journal for immunotherapy of cancer · 2026Article
- ASB2 inhibits lipid accumulation to promote ILC1 homeostatic fitness and anti-tumor immunity in the mouse liver.Nature communications · 2026Article
- Interactions Between Circulating Tumor Cells and the Immune System in Colorectal Cancer: Friends or Foes?Cancers · 2026Review
- Stem cell-based tactics in the remodeling and treatment of intestinal diseases.Stem cell research & therapy · 2026Review
- Combining AI to reveal CCDC3-mediated pathways of colorectal cancer liver metastasis.NPJ digital medicine · 2026Article
- Macrophage-rich niches regulate T cell dynamics at the liver invasive margin during gallbladder cancer progression.The Journal of clinical investigation · 2026Article
- Targeting Microglial CD49a Inhibits Neuroinflammation and Demonstrates Therapeutic Potential for Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Colorectal cancer liver metastasis: immunosuppressive microenvironment, signaling pathways, and emerging therapeutic strategies.Frontiers in immunology · 2026Review
- Liver microenvironment-driven immunosuppressive niche in colorectal cancer liver metastasis and its therapeutic remodeling.Frontiers in immunology · 2026Review
- A CCL4-enriched NK-cell transcriptional state is associated with inflammatory and myeloid-stromal programs in colorectal cancer liver metastasis.Frontiers in immunology · 2026Article
- Navigating the Tumor Microenvironment in Colorectal Liver Metastasis: Barriers to Therapy and Emerging Opportunities.Oncology research · 2026Review
- CXCR3 gene as a therapeutic target in colorectal cancer.BMC cancer · 2025Article
- The hepatic macrophage: a key regulator of liver metastatic tumor microenvironment through cell crosstalk.Journal of translational medicine · 2025Review
- CC/CXC chemokine risk signature at single-cell resolution: a machine learning model for precision stratification in cervical cancer.Translational cancer research · 2025Article
- The role of NK cells in regulating tumorimmunity: current state, challenges and future strategies.Cancer cell international · 2025Review
- Liver metastasis of colorectal cancer: Mechanism and clinical therapy (Review).Oncology reports · 2025Review
- Liver regeneration-associated hepatocellular YAP1 activation prevents colorectal cancer liver metastasis through glutamine competition.Science advances · 2025Article
- Enhanced homing and efficacy of HER2-CAR T cells via CXCR5/CCR6 co-expression for HER2-positive NSCLC.Journal of translational medicine · 2025Article
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Authors and funding
19 authors.
Funding
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Abstract
The antimetastatic activity of NK cells is well established in several cancer types, but the mechanisms underlying NK cell metastasis infiltration and acquisition of antitumor characteristics remain unclear. Herein, we investigated the cellular and molecular factors required to facilitate the generation of an ILC1-like CD49a+ NK cell population within the liver metastasis (LM) environment of colorectal cancer (CRC). We show that CD49a+ NK cells had the highest cytotoxic capacity among metastasis-infiltrating NK cells in the MC38 mouse model. Furthermore, the chemokine receptor CXCR3 promoted CD49a+ NK cell accumulation and persistence in metastasis where NK cells colocalize with macrophages in CXCL9- and CXCL10-rich areas. By mining a published scRNA-seq dataset of a cohort of patients with CRC who were treatment naive, we confirmed the accumulation of CXCR3+NK cells in metastatic samples. Conditional deletion of Cxcr3 in NKp46+ cells and antibody-mediated depletion of metastasis-associated macrophages impaired CD49a+NK cell development, indicating that CXCR3 and macrophages contribute to efficient NK cell localization and polarization in LM. Conversely, CXCR3neg NK cells maintained a CD49a- phenotype in metastasis with reduced parenchymal infiltration and tumor killing capacity. Furthermore, CD49a+ NK cell accumulation was impaired in an independent SL4-induced CRC metastasis model, which fails to accumulate CXCL9+ macrophages. Together, our results highlight a role for CXCR3/ligand axis in promoting macrophage-dependent NK cell accumulation and functional sustenance in CRC LM.
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