ArticleJournal for immunotherapy of cancer2019
Characterization of immune responses to anti-PD-1 mono and combination immunotherapy in hematopoietic humanized mice implanted with tumor xenografts.
Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
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
130 citing papers in PubMed, 1 synthesis or guideline pooled it, 173 citations in OpenAlex.
- Pooled it
- Phase II Clinical Trial and Preclinical Evaluation of a Novel CD47 Blockade Combination in Refractory Microsatellite-Stable Metastatic Colorectal Cancer.Cancer research communications · 2025Trial
- Interleukin-1 receptor-associated kinase 1 controls chemoresistance and immuno-killing in non-small cell lung cancer.Signal transduction and targeted therapy · 2026Article
- Humanized immune system animal models and their recent applications.Animal models and experimental medicine · 2026Review
- PRKN mediates the ubiquitination of SCAF8 to reduce the mRNA stability of KLF5 and its transcriptional activation of EFNA3 in colorectal cancer.Cellular & molecular biology letters · 2026Article
- Nephrotoxicity of Immune Checkpoint Inhibitors in Mice with a Human Immune System.bioRxiv : the preprint server for biology · 2026Article
- Tumors hijack immune-privileging regulons via distinct cell types to confer T cell desertion and immunotherapy resistance across various cancers.Nature communications · 2026Article
- IMIREG: a lineage-resolved regulon signature unveiling immune engagement archetypes and predicting immunotherapy response across diverse cancers.NPJ precision oncology · 2026Article
- Humanized avian embryo models replicate an immune tumor environment for rapid immunotherapy studies.EMBO molecular medicine · 2026Article
- A novel humanized immune stroma PDX cancer model for therapeutic studies.Cancer immunology, immunotherapy : CII · 2026Article
- Preclinical models of breast cancer metastasis: strengths, limitations, and clinical relevance.NPJ breast cancer · 2026Review
- The application of experimental models for the drug discovery for digestive tumors.Molecular cancer · 2026Review
- Harnessing PDX and PDX 2.0: the next-generation paradigm for precision oncology and translational breakthroughs.Molecular cancer · 2026Review
- LSD1 Inhibition Induces MHC-I and Dendritic Cell Activation to Promote Antitumor Immunity in Head and Neck Squamous Cell Carcinoma.Cancer research · 2026Article
- Immuno-radiotherapy enhances tumor control and induces abscopal responses in a humanized mouse model.Frontiers in immunology · 2026Article
- Nanomedicine-Based Therapeutic Approaches in Colorectal Cancer Using Patient-Derived Xenograft Models: Prospects and Challenges.International journal of nanomedicine · 2026Review
- Modulation of CCL5 and CXCR4 as EMT signaling biomarkers by cold atmospheric plasma and Anti-PD-1 combination therapy in melanoma: Insights from integrated bioinformatics andIranian journal of basic medical sciences · 2026Article
- Discovery of tumor antigens in renal cell carcinoma and prospects for clinical application.Frontiers in immunology · 2026Review
- Spontaneous cSCC Murine Model Shows Limited Response to PD-1 Blockade and Radiation Combination Therapy.Cancers · 2025Article
- Monitoring systemic immune responses to checkpoint inhibition in breast cancer reveals host responses and mechanisms of resistance.Journal for immunotherapy of cancer · 2025Article
70 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundThe success of agents that reverse T-cell inhibitory signals, such as anti-PD-1/PD-L1 therapies, has reinvigorated cancer immunotherapy research. However, since only a minority of patients respond to single-agent therapies, methods to test the potential anti-tumor activity of rational combination therapies are still needed. Conventional murine xenograft models have been hampered by their immune-compromised status; thus, we developed a hematopoietic humanized mouse model, hu-CB-BRGS, and used it to study anti-tumor human immune responses to triple-negative breast cancer (TNBC) cell line and patient-derived colorectal cancer (CRC) xenografts (PDX).
methodsBALB/c-Rag2
resultsHumanized PDX models were successfully established with a high frequency of tumor engraftment. Humanized mice treated with anti-PD-1 exhibited increased anti-tumor human T-cell responses coupled with decreased Treg and myeloid populations that correlated with tumor growth inhibition. Combination therapies with anti-PD-1 treatment in TNBC-bearing mice reduced tumor growth in multi-drug cohorts. Finally, as observed in human colorectal patients, anti-PD-1 therapy had a strong response to a microsatellite-high CRC PDX that correlated with a higher number of human CD8+ IFNγ+ T cells in the tumor.
conclusionHu-CB-BRGS mice represent an in vivo model to study immune checkpoint blockade to human tumors. The human immune system in the mice is inherently suppressed, similar to a tumor microenvironment, and thus allows growth of human tumors. However, the suppression can be released by anti-PD-1 therapies and inhibit tumor growth of some tumors. The model offers ample access to lymph and tumor cells for in-depth immunological analysis. The tumor growth inhibition correlates with increased CD8 IFNγ+ tumor infiltrating T cells. These hu-CB-BRGS mice provide a relevant preclinical animal model to facilitate prioritization of hypothesis-driven combination immunotherapies.
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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.