ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020
Generation of Genetically Engineered Mouse Lung Organoid Models for Squamous Cell Lung Cancers Allows for the Study of Combinatorial Immunotherapy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 2 of them syntheses that pooled it.
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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
48 citing papers in PubMed, 2 syntheses or guidelines pooled it, 73 citations in OpenAlex.
- A systematic review on the culture methods and applications of 3D tumoroids for cancer research and personalized medicine.Cellular oncology (Dordrecht, Netherlands) · 2025Pooled it
- Applications of lung cancer organoids in precision medicine: from bench to bedside.Cell communication and signaling : CCS · 2023Pooled it
- MiR-1976 affects lung squamous cell carcinoma development by targeting NCAPH.Journal of applied genetics · 2026Article
- Review
- Generation of a stable mouse endometrial tumor-derived cell line using conditional reprogramming.Biological research · 2026Article
- Application of organoid models in basic and translational research of lung cancer: a narrative review.Translational lung cancer research · 2026Review
- Research Advances and Disease Modeling in Respiratory Organoids.Biomedicines · 2026Review
- 3D models for cancer-microbe interaction studiesFrontiers in immunology · 2026Article
- Modeling metastasis - leveraging novel tools to streamline discovery in advanced cancer.Disease models & mechanisms · 2025Review
- Targeting mTORC2 in lung squamous cell carcinoma improves anti-tumor immunity through the PSGL-1-VISTA axis.Cancer gene therapy · 2025Article
- Organoid models in oncology: advancing precision cancer therapy and vaccine development.Cancer biology & medicine · 2025Review
- Tumor suppressors in Sox2-mediated lung cancers promote distinct cell-intrinsic and immunologic remodeling.JCI insight · 2025Article
- Article
- Squamous cell cancers of the aero-upper digestive tract: A unified perspective on biology, genetics, and therapy.Cancer cell · 2025Review
- [Prospects of Smoking Hazards Research Using Lung Organoid].Jugan geon-gang gwa jilbyeong · 2025Review
- Progress and prospects of organoids in the pathogenesis of lung cancer and screening of antitumor drugs.Frontiers in oncology · 2025Review
- AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis.Science China. Life sciences · 2025Article
- Review
- Unveiling the functional roles of patient-derived tumour organoids in assessing the tumour microenvironment and immunotherapy.Clinical and translational medicine · 2024Review
- TET2-STAT3-CXCL5 nexus promotes neutrophil lipid transfer to fuel lung adeno-to-squamous transition.The Journal of experimental medicine · 2024Article
Corrections and comments
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Authors and funding
21 authors at 2 institutions in 1 country.
Funding
Abstract
purposeLung squamous cell carcinoma (LSCC) is a deadly disease for which only a subset of patients responds to immune checkpoint blockade (ICB) therapy. Therefore, preclinical mouse models that recapitulate the complex genetic profile found in patients are urgently needed. EXPERIMENTAL
designWe used CRISPR genome editing to delete multiple tumor suppressors in lung organoids derived from Cre-dependent SOX2 knock-in mice. We investigated both the therapeutic efficacy and immunologic effects accompanying combination PD-1 blockade and WEE1 inhibition in both mouse models and LSCC patient-derived cell lines.
resultsWe show that multiplex gene editing of mouse lung organoids using the CRISPR-Cas9 system allows for efficient and rapid means to generate LSCCs that closely mimic the human disease at the genomic and phenotypic level. Using this genetically defined mouse model and three-dimensional tumoroid culture system, we show that WEE1 inhibition induces DNA damage that primes the endogenous type I IFN and antigen presentation system in primary LSCC tumor cells. These events promote cytotoxic T-cell-mediated clearance of tumor cells and reduce the accumulation of tumor-infiltrating neutrophils. Beneficial immunologic features of WEE1 inhibition are further enhanced by the addition of anti-PD-1 therapy.
conclusionsWe developed a mouse model system to investigate a novel combinatory approach that illuminates a clinical path hypothesis for combining ICB with DNA damage-inducing therapies in the treatment of LSCC.
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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 Socratic graph.