ArticleFrontiers in immunology2020
The Tumor Milieu Promotes Functional Human Tumor-Resident Plasmacytoid Dendritic Cells in Humanized Mouse Models.
Article in Frontiers in immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- Stepwise Evolution of Immunodeficient Mouse Models: Focus on NCG Strains and Their Applications in Humanized Immune System Research.Vaccines · 2026Review
- Nuclear RSK1 mediates interferon-γ-induced proinflammatory activation in human primary macrophages and humanized mice.Science advances · 2026Article
- Humanized immune system animal models and their recent applications.Animal models and experimental medicine · 2026Review
- Pathology associated with human CAR T cell administration in NOD.Cg-Veterinary pathology · 2026Article
- Testing the capacity of humanized immune system mice to induce a protective antibody response against the Lyme disease pathogen.Microbiology spectrum · 2026Article
- Patient-Derived Models of Liver Cancer to Inform Clinical Treatment Paradigms: Recent Updates.Seminars in liver disease · 2026Review
- Immuno-radiotherapy enhances tumor control and induces abscopal responses in a humanized mouse model.Frontiers in immunology · 2026Article
- A comprehensive analysis of humanized mouse models for the study of cancer immunotherapies.Frontiers in immunology · 2026Article
- Development of humanized mouse models for the preclinical evaluation of NK cell-based therapies.Frontiers in immunology · 2026Article
- Humanized mouse models in MDS.Cell death & disease · 2025Review
- Diagnostic challenge in veterinary pathology: Otitis in a humanized NOG-EXL mouse.Veterinary pathology · 2025Article
- Human GM-CSF/IL-3 enhance tumor immune infiltration in humanized HCC patient-derived xenografts.JHEP reports : innovation in hepatology · 2025Article
- Tumor-dependent myeloid and lymphoid cell recruitment in genO-BRGSF-HIS mice: a novel tool for evaluating immunotherapies.Frontiers in immunology · 2025Article
- Disabled-2, a versatile tissue matrix multifunctional scaffold protein with multifaceted signaling: Unveiling its potential in the cancer battle.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Humanization with CD34-positive hematopoietic stem cells in NOG-EXL mice results in improved long-term survival and less severe myeloid cell hyperactivation phenotype relative to NSG-SGM3 mice.Veterinary pathology · 2024Article
- Fetal liver CD34Stem cell research & therapy · 2024Article
- Article
- Modeling the Tumor Microenvironment and Cancer Immunotherapy in Next-Generation Humanized Mice.Cancers · 2023Review
- PMN-MDSCs modulated by CCL20 from cancer cells promoted breast cancer cell stemness through CXCL2-CXCR2 pathway.Signal transduction and targeted therapy · 2023Article
- Humanized mouse models for immuno-oncology research.Nature reviews. Clinical oncology · 2023Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Particular interest to harness the innate immune system for cancer immunotherapy is fueled by limitations of immune checkpoint blockade. Plasmacytoid dendritic cells (pDC) are detected in a variety of solid tumors and correlate with poor clinical outcome. Release of type I interferons in response to toll-like-receptor (TLR)7 and TLR9 activation is the pDC hallmark. Mouse and human pDC differ substantially in their biology concerning surface marker expression and cytokine production. Here, we employed humanized mouse models (HIS) to study pDC function. We performed a comprehensive characterization of transgenic, myeloid-enhanced mouse strains (NOG-EXL and NSG-SGM3) expressing human interleukin-3 (hIL-3) and granulocyte-macrophage colony stimulating factor (GM-CSF) using identical humanization protocols. Only in HIS-NOG-EXL mice sufficient pDC infiltration was detectable. Therefore, we selected this strain for subsequent tumor studies. We analyzed pDC frequency in peripheral blood and tumors by comparing HIS-NOG-EXL with HIS-NOG mice bearing three different ovarian and breast tumors. Despite the substantially increased pDC numbers in peripheral blood of HIS-NOG-EXL mice, we detected TLR7/8 agonist responsive and thus functional pDCs only in certain tumor models independent of the mouse strain employed. However, HIS-NOG-EXL mice showed in general a superior humanization phenotype characterized by reconstitution of different myeloid subsets, NK cells and B cells producing physiologic IgG levels. Hence, we provide first evidence that the tumor milieu but not genetically introduced cytokines defines intratumoral (i.t.) frequencies of the rare pDC subset. This study provides model systems to investigate
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