ArticleThe Journal of clinical investigation2023
In situ expansion and reprogramming of Kupffer cells elicit potent tumoricidal immunity against liver metastasis.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 44 citations in OpenAlex.
- Research on tissue-resident macrophages in the field of cancer research: a bibliometric analysis from 2004 to 2025.Cell adhesion & migration · 2026Review
- Niches in cancer: from primary tumors to metastatic disease.Journal of hematology & oncology · 2026Review
- Microenvironment-Driven Reprogramming in Colorectal Cancer Liver Metastasis: Metabolic, Phenotypic, and Immune Adaptation.International journal of molecular sciences · 2026Review
- Kupffer cells in liver homeostasis and disease: from immune sentinels to metabolic gatekeepers.Nature reviews. Immunology · 2026Review
- Gene therapy for liver diseases: methods, challenges and opportunities.Journal of nanobiotechnology · 2026Review
- Preoperative exercise induces anti-tumor Kupffer cells to prevent surgical stress-promoted colorectal cancer liver metastasis.Cell reports. Medicine · 2026Article
- Colorectal cancer liver metastasis: immunosuppressive microenvironment, signaling pathways, and emerging therapeutic strategies.Frontiers in immunology · 2026Review
- Colorectal cancer liver metastases: mechanism and therapy.Frontiers in immunology · 2026Review
- Impact of hepatic radiotherapy on survival and safety outcomes in small cell lung cancer patients with liver metastases: a retrospective study.Therapeutic advances in medical oncology · 2026Article
- Targeting innate immunity in cancer: mechanistic foundations, therapeutic vaccination, and clinical translation.Frontiers in immunology · 2026Review
- Convergent systemic therapy for liver metastases: Bridging primary tumor heterogeneity through shared pathways.iLIVER · 2025Review
- The hepatic macrophage: a key regulator of liver metastatic tumor microenvironment through cell crosstalk.Journal of translational medicine · 2025Review
- Viral-Directed Augmentation of Kupffer Cell Cross-Presentation Provokes Antitumor Immunity Against Liver Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- VSIG4 Is Dispensable for Tumor Growth and Metastasis in Murine Colorectal and Breast Cancer Models.Cancers · 2025Article
- Metastatic hepatic carcinoma: Mechanisms, emerging therapeutics, and future perspectives.iScience · 2025Review
- Decoding metastatic microenvironments through single-cell omics reveals new insights into niche dynamics and tumor evolution.PLoS biology · 2025Article
- Heterogeneous tissue-specific macrophages orchestrate metastatic organotropism of breast cancer: implications for promising therapeutics.Journal of translational medicine · 2025Review
- Review
- CXFrontiers in immunology · 2025Article
- Visualizing cellular interactions: intravital imaging in tumor microenvironment.Frontiers in immunology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liver metastasis represents one of the most frequent malignant diseases with no effective treatment. Functional reprogramming of Kupffer cells (KCs), the largest population of hepatic macrophages, holds promise for treating liver cancer, but remains seldom exploited. Taking advantage of the superior capacity of KCs to capture circulating bacteria, we report that a single administration of attenuated Escherichia coli producing clustered regularly interspersed short palindromic repeats CasΦ (CRISPR/CasΦ) machinery enables efficient editing of genes of interest in KCs. Using intravital microscopy, we observed a failure of tumor control by KCs at the late stage of liver metastasis due to KC loss preferentially in the tumor core and periphery, resulting in inaccessibility of these highly phagocytic macrophages to cancer cells. Simultaneous disruption of MafB and c-Maf expression using the aforementioned engineered bacteria could overcome KC dysfunction and elicit remarkable curative effects against several types of metastatic liver cancer in mice. Mechanistically, bacterial treatment induced massive proliferation and functional reprogramming of KCs. These cells infiltrated into the tumor, dismantled macrometastases by nibbling cancer cells, and skewed toward proinflammatory macrophages to unleash antitumor T cell responses. These findings provide an immunotherapy strategy that could be applicable for treating liver metastasis and highlight the therapeutic potential of targeting tissue-resident macrophages in cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.