ArticleCancer research2022
An Immunogenic Model of KRAS-Mutant Lung Cancer Enables Evaluation of Targeted Therapy and Immunotherapy Combinations.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 2 of them syntheses that pooled it.
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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
56 citing papers in PubMed, 2 syntheses or guidelines pooled it, 75 citations in OpenAlex.
- KRASFrontiers in oncology · 2026Pooled it
- Phase IV clinical trials for the treatment of non-small cell lung carcinoma (NSCLC): A systemic review from 2020-2025.Saudi medical journal · 2025Pooled it
- CD137 agonists in mice suppress germinal center responses by increasing the immunosuppressive activity of follicular regulatory T-cells.The EMBO journal · 2026Article
- Coordinated Immune Activation Following KRAS Inhibition in Syngeneic Models Reveals Molecular Pathways that Potentiate and Limit Antitumor Immunity.Cancer immunology research · 2026Article
- KRAS Inhibitor-Induced Cancer Cell Death Enhances Sensitivity to Immune-Mediated Bystander Killing of Drug-Resistant Subclones.Cancer research · 2026Article
- Endoglin (CD105) overexpression is associated with an immunosuppressive tumor microenvironment in murine lung cancer models and human lung adenocarcinoma.Scientific reports · 2026Article
- Abrogation of Oncogenic RAS Signaling by a RAS(ON) Inhibitor Doublet Primes Immune-Refractory KRASG12C-Mutant NSCLC for Immune Checkpoint Blockade.Cancer discovery · 2026Article
- Argonaute 2 drives resistance to immune checkpoint inhibitors in immunorefractory non-small cell lung cancer.PLoS biology · 2026Article
- Article
- Impact of particulate matter 2.5 on a mouse model of lung adenocarcinoma.BMC pulmonary medicine · 2026Article
- KRAS Inhibitors in Pancreas Cancer: Facts and Hopes about the Immunotherapy We Have All Been Waiting for.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- HIF-1αImmunity · 2026Article
- WNT inhibition activates interferon stimulated gene expression by alleviating epigenetic repression of endogenous retroviruses.Scientific reports · 2026Article
- Lung-targeted RNA delivery systems: strategies and therapeutic applications.Journal of nanobiotechnology · 2026Review
- Correlation between tumor mutational burden and CT radiographic features in EGFR exon 19 deletion-mutated lung adenocarcinoma: a diagnostic accuracy study.Frontiers in medicine · 2026Article
- Targeting KRAS mutations: orchestrating cancer evolution and therapeutic challenges.Signal transduction and targeted therapy · 2025Review
- Article
- Development and characterisation of improved unifocal primary mouse lung cancer models with metastatic potential.The Journal of pathology · 2025Article
- Blocking Nitrosylation Induces Immunogenic Cell Death by Sensitizing NRAS-Mutant Melanoma to MEK Inhibitors.Cancer research · 2025Article
- Tissue-specific properties of type 1 dendritic cells in lung cancer: implications for immunotherapy.Journal for immunotherapy of cancer · 2025Review
Corrections and comments
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Authors and funding
26 authors at 5 institutions in 2 countries.
Funding
Abstract
Mutations in oncogenes such as KRAS and EGFR cause a high proportion of lung cancers. Drugs targeting these proteins cause tumor regression but ultimately fail to elicit cures. As a result, there is an intense interest in how to best combine targeted therapies with other treatments, such as immunotherapies. However, preclinical systems for studying the interaction of lung tumors with the host immune system are inadequate, in part due to the low tumor mutational burden in genetically engineered mouse models. Here we set out to develop mouse models of mutant KRAS-driven lung cancer with an elevated tumor mutational burden by expressing the human DNA cytosine deaminase, APOBEC3B, to mimic the mutational signature seen in human lung cancer. This failed to substantially increase clonal tumor mutational burden and autochthonous tumors remained refractory to immunotherapy. However, establishing clonal cell lines from these tumors enabled the generation of an immunogenic syngeneic transplantation model of KRAS-mutant lung adenocarcinoma that was sensitive to immunotherapy. Unexpectedly, antitumor immune responses were not directed against neoantigens but instead targeted derepressed endogenous retroviral antigens. The ability of KRASG12C inhibitors to cause regression of KRASG12C -expressing tumors was markedly potentiated by the adaptive immune system, highlighting the importance of using immunocompetent models for evaluating targeted therapies. Overall, this model provides a unique opportunity for the study of combinations of targeted and immunotherapies in immune-hot lung cancer. SIGNIFICANCE: This study develops a mouse model of immunogenic KRAS-mutant lung cancer to facilitate the investigation of optimal combinations of targeted therapies with 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.