ArticleCell reports2023
KEAP1 mutation in lung adenocarcinoma promotes immune evasion and immunotherapy resistance.
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Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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113citing papers in PubMed
26.2field-weighted citation impact, top 1% of its field
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Who cites it
113 citing papers in PubMed, 114 citations in OpenAlex.
- Trial
- Evaluation of Biomarkers for Sacituzumab Govitecan in Metastatic Non-Small Cell Lung Cancer: Insights From the EVOKE-01 Study.Cancer research communications · 2026Trial
- Gut microbiota-derived metabolites as context-dependent modulators of Nrf2 signaling in inflammation-driven carcinogenesis.Gut microbes · 2026Review
- Tumor cell-intrinsic stress states drive sensitivity to CAR T cell therapy in pancreatic cancer.Science advances · 2026Article
- SMARCA4, STK11, and KEAP1 co-inactivation associates with poor prognosis and upregulation of the TGF-β pathway in lung adenocarcinoma.Translational oncology · 2026Article
- Downregulation of SELENOS Suppresses the Progression of Renal Cell Carcinoma by Activating Ferroptosis.Biological trace element research · 2026Article
- Pharmacogenomics in oncology: mutation-targeted therapy and biomarker integration in non-small cell lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Article
- Targeted KEAP1 disruption enhances antioxidant defense and mesenchymal stromal cell therapy for chronic limb-threatening ischemia.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- LIF-Induced Tumor Plasticity Establishes an Immunosuppressive Myeloid Niche in LKB1-Mutant Lung Cancer.Cancer discovery · 2026Article
- Tumor suppressor genotype influences the extent and mode of immunosurveillance in lung cancer.Nature communications · 2026Article
- Clinicopathological characteristics of patients with inoperable non-small cell lung cancer harboring circulating NRF2 pathway mutations.The Journal of pathology · 2026Article
- Integrated analysis of scRNA-seq and bulk RNA-seq identifies matrisome-related biomarkers for prognostic stratification and immune landscape in lung adenocarcinoma.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- Turning KEAP1 against NRF2.Nature chemical biology · 2026Article
- cGAS-STING pathway in lung cancer and emerging therapeutic approaches.Drug discovery today · 2026Review
- Multi-Omics reveals SPP1 + malignant and CXCR4Discover oncology · 2026Article
- XAF1 nonsense mutation rs117407731 enhances lung adenocarcinoma susceptibility via apoptosis suppression.Molecular genetics and genomics : MGG · 2026Article
- Review
- RAS signaling in lung adenocarcinoma is defined by lineage context and DUSP4 loss.JCI insight · 2026Article
53 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 7 institutions in 2 countries.
Anastasia-Maria ZavitsanouDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, USA; Vilcek Institute of Graduate Biomedical Sciences, NYU Grossman School of Medicine, New York, NY, USA.
Ray PillaiDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, USA; Division of Pulmonary and Critical Care Medicine, Department of Medicine, VA New York Harbor Healthcare System, New York, NY, USA; Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, NYU Grossman School of Medicine, New York, NY, USA.
Yuan HaoApplied Bioinformatics Laboratories, NYU Grossman School of Medicine, New York, NY, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY, USA.
Warren L WuDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, USA; Vilcek Institute of Graduate Biomedical Sciences, NYU Grossman School of Medicine, New York, NY, USA.
Eric BartnickiVilcek Institute of Graduate Biomedical Sciences, NYU Grossman School of Medicine, New York, NY, USA; Department of Microbiology, NYU Grossman School of Medicine, New York, NY, USA.
Triantafyllia KarakousiDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, USA; Vilcek Institute of Graduate Biomedical Sciences, NYU Grossman School of Medicine, New York, NY, USA.
Sahith RajalingamDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, USA.
Alberto HerreraDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, USA; Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY, USA.
Angeliki KaratzaDivision of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, NYU Grossman School of Medicine, New York, NY, USA.
Ali RashidfarrokhiDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, USA; Vilcek Institute of Graduate Biomedical Sciences, NYU Grossman School of Medicine, New York, NY, USA.
Sabrina SolisVilcek Institute of Graduate Biomedical Sciences, NYU Grossman School of Medicine, New York, NY, USA; NYU Langone Vaccine Center, NYU Grossman School of Medicine, New York, NY, USA.
Metamia CiampricottiDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Anna H YeatonDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY, USA.
Ellie IvanovaDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, USA.
Corrin A WohlhieterMolecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Terkild B BuusDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, USA; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Makiko HayashiDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, USA.
Burcu Karadal-FerrenaDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, USA.
Harvey I PassDepartment of Cardiothoracic Surgery, NYU Langone Health, New York, NY, USA.
John T PoirierLaura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY, USA.
Charles M RudinDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Kwok-Kin WongLaura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY, USA.
Andre L MoreiraDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, USA.
Kamal M KhannaDivision of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, NYU Grossman School of Medicine, New York, NY, USA; Department of Microbiology, NYU Grossman School of Medicine, New York, NY, USA.
Aristotelis TsirigosDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, USA; Division of Pulmonary and Critical Care Medicine, Department of Medicine, VA New York Harbor Healthcare System, New York, NY, USA; Institute for Computational Medicine, NYU Grossman School of Medicine, New York, NY, USA.
Thales PapagiannakopoulosDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY, USA. Electronic address: thales.papagiannakopoulos@nyulangone.org.
Sergei B KoralovDepartment of Pathology, NYU Grossman School of Medicine, New York, NY, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY, USA. Electronic address: sergei.koralov@nyulangone.org.
New York University · USNYU Langone’s Laura and Isaac Perlmutter Cancer CenterMemorial Sloan Kettering Cancer Center · USVA NY Harbor Healthcare System · USCornell University · USNYU Langone Health · USUniversity of Copenhagen · DK
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MVaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ANIRBAN MAITRA · 1985 to 2026
$83.1MMEDICAL SCIENTIST TRAININGT32GM007308 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI PHILIPS, MARK REID · 1985 to 2019
$23.2MThe impact of changes in chromatin architecture on cancer phenotypes and tumor progressionP01CA229086 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ADRIANA HEGUY · 2019 to 2026
$17.0MTRAINING PROGRAM IN MOLECULAR ONCOLOGY &IMMUNOLOGYT32CA009161 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI CARROLL, WILLIAM L., LEVY, DAVID E · 1985 to 2020
$13.3MTraining Program in Immunology and Inflammation.T32AI100853 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Susan Ruth Schwab · 2012 to 2026
$4.5MTargeting Epigenetic Heterogeneity in Pediatric T cell leukemia: Epi-Clones as Drivers of ChemoresistanceR01CA252239 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Aristotelis Tsirigos · 2021 to 2026
$3.7MNovel lung resident interstitial macrophage subset with distinct localization and polarizationR01AI143861 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KHANNA, KAMAL MOHAN · 2019 to 2023
$3.3MIdentifying metabolic dependencies in genetic subtypes of KRAS-driven lung cancerR37CA222504 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI PAPAGIANNAKOPOULOS, THALES · 2018 to 2024
$3.3MMicrobial triggers and molecular mechanisms of Th17 mediated airway inflammation-Resubmission-1R01HL125816 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KORALOV, SERGEI BORISOVICH · 2015 to 2019
$3.3MRole of S.aureus in Cutaneous T Cell Lymphoma PathogenesisR01CA271245 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Sergei Borisovich Koralov · 2022 to 2026
$2.7MUncovering Genotype Specific Vulnerabilities in KRAS Mutant Lung Cancer?R01CA227649 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI PAPAGIANNAKOPOULOS, THALES · 2018 to 2022
$1.9MNCI NIH HHS F30 CA247020NCI NIH HHS P01 CA229086NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA016087NCI NIH HHS R01 CA227649NCI NIH HHS R01 CA252239NCI NIH HHS R01 CA271245NCI NIH HHS R37 CA222504NCI NIH HHS T32 CA009161NHLBI NIH HHS R01 HL125816NIAID NIH HHS R01 AI143861NIAID NIH HHS T32 AI100853NIGMS NIH HHS T32 GM007308
Abstract
Lung cancer treatment has benefited greatly through advancements in immunotherapies. However, immunotherapy often fails in patients with specific mutations like KEAP1, which are frequently found in lung adenocarcinoma. We established an antigenic lung cancer model and used it to explore how Keap1 mutations remodel the tumor immune microenvironment. Using single-cell technology and depletion studies, we demonstrate that Keap1-mutant tumors diminish dendritic cell and T cell responses driving immunotherapy resistance. This observation was corroborated in patient samples. CRISPR-Cas9-mediated gene targeting revealed that hyperactivation of the NRF2 antioxidant pathway is responsible for diminished immune responses in Keap1-mutant tumors. Importantly, we demonstrate that combining glutaminase inhibition with immune checkpoint blockade can reverse immunosuppression, making Keap1-mutant tumors susceptible to immunotherapy. Our study provides new insight into the role of KEAP1 mutations in immune evasion, paving the way for novel immune-based therapeutic strategies for KEAP1-mutant cancers.
Indexed as
Adenocarcinoma of LungLung NeoplasmsCell Line, TumorHumansImmune EvasionImmunotherapyKelch-Like ECH-Associated Protein 1MutationNF-E2-Related Factor 2Tumor MicroenvironmentKEAP1 protein, humanKelch-Like ECH-Associated Protein 1NF-E2-Related Factor 2adenocarcinomaCD103 DCCP: CancerCP: Immunologyimmune surveillanceimmunotherapyKEAP1LUADlung cancerNRF2NSCLCT cell
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