ArticleCancer cell2014
Loss of Lkb1 and Pten leads to lung squamous cell carcinoma with elevated PD-L1 expression.
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Article in Cancer cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 245 papers, 1 of them a synthesis that pooled it.
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245citing papers in PubMed, 1 pooled it
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Who cites it
245 citing papers in PubMed, 1 synthesis or guideline pooled it, 381 citations in OpenAlex.
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- Phase II Trial of Pembrolizumab after High-Dose Cytarabine in Relapsed/Refractory Acute Myeloid Leukemia.Blood cancer discovery · 2021Trial
- The PD-L1-mTOR intersection in tumor migration and invasion.Molecular biology reports · 2026Review
- ClonalLife science alliance · 2026Article
- Molecular insights and therapeutic implications for the tumor suppressor role of LKB1 in non-small cell lung cancer.Cancer letters · 2026Review
- EZH1/2 inhibition improves immunotherapy response through MHC Class II de-repression and neutrophil reprogramming.bioRxiv : the preprint server for biology · 2026Article
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- A Non-Canonical Role of SMAD4 in Regulating 3D Genome Architecture to Inhibit Lung Squamous Cell Carcinoma Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- IKKβ and USP28 Regulate HEY1 Stability to Promote Cancer Stemness and Immune Evasion in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- KAT2A-IGF2BP1-CXCL2 axis in the high lactate tumor microenvironment facilitates resistance to anti-PD-1 therapy in lung adenocarcinoma by recruiting myeloid-derived suppressor cells.Cell death & disease · 2026Article
- Insight of immune checkpoint blockades in melanoma: mechanism and clinical translation.Molecular cancer · 2026Review
- Bcl-xL blockade targets neutrophils and synergizes with chemotherapy in lung squamous cell carcinoma.EMBO molecular medicine · 2026Article
- Coordinated Multicellular Immune Programs and Drug Targets Revealed by Single-Cell Analysis in Driver-Mutated NSCLC.International journal of molecular sciences · 2026Article
- Strategies to target PD-1/PD-L1 in the tumor microenvironment.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- TET2: a critical regulatory hub with broad therapeutic implications across human diseases.Frontiers in immunology · 2026Review
- Mast cell driven immunometabolism as a therapeutic entry point in ESCC.Frontiers in cell and developmental biology · 2026Review
- Targeting Phosphatase and Tensin Homolog Deleted on Chromosome 10q23.3 (PTEN) as a Potential Theragnostic Biomarker in Tumors.Recent patents on anti-cancer drug discovery · 2026Article
- TMPRSS11B promotes an acidified microenvironment and immune suppression in squamous lung cancer.EMBO reports · 2025Article
- Combined CHK1 and PD-L1 blockade as a novel therapeutic strategy against stemness and immunosuppression in ovarian cancer.Cancer immunology, immunotherapy : CII · 2025Article
- Unraveling the molecular-pathological characteristics and cellular complexity of the tumor immune microenvironment in metastatic non-small cell lung cancer.Cell communication and signaling : CCS · 2025Review
185 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors at 10 institutions in 2 countries.
Chunxiao XuDepartment of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Belfer Institute For Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Christine M FillmoreStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Shohei KoyamaDepartment of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Hongbo WuDepartment of Internal Medicine, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China.
Yanqiu ZhaoDepartment of Internal Medicine, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China.
Zhao ChenDepartment of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Belfer Institute For Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Grit S Herter-SprieDepartment of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Belfer Institute For Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Esra A AkbayDepartment of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Belfer Institute For Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Jeremy H TchaichaDepartment of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Belfer Institute For Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Abigail AltabefDepartment of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Belfer Institute For Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Jacob B ReibelDepartment of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Belfer Institute For Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Zandra WaltonAbramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Hongbin JiState Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Hideo WatanabeDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Cancer Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Pasi A JänneDepartment of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Belfer Institute For Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Diego H CastrillonDepartment of Pathology and Simmons Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Anil K RustgiDivision of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Adam J BassDepartment of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Cancer Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Gordon J FreemanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Robert F PaderaDepartment of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Glenn DranoffDepartment of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Peter S HammermanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Cancer Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: phammerman@partners.org.
Carla F KimStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: carla.kim@childrens.harvard.edu.
Kwok-Kin WongDepartment of Medicine, Harvard Medical School, Boston, MA 02115, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Belfer Institute For Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: kwong1@partners.org.
Dana-Farber Cancer Institute · USHarvard University · USBroad Institute · USUniversity of Pennsylvania · USBrigham and Women's Hospital · USCenter for Excellence in Molecular Cell Science · CNHarvard Stem Cell Institute · USHenan Cancer Hospital · CNSouthwestern Medical Center · USZhengzhou University · CN
Funding
Tuberous Sclerosis-Pathway and PathogenesisP01CA120964 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI David J. Kwiatkowski · 2007 to 2026
$35.9MTransformed Esophageal Epithelial Cells and the Tumor MicroenvironmentP01CA098101 · NCI · UNIVERSITY OF PENNSYLVANIA · PI DIEHL, JOHN ALAN · 2003 to 2023
$31.7MStructureP01CA154303 · NCI · DANA-FARBER CANCER INST · PI JANNE, PASI A · 2012 to 2021
$17.8MMicroenvironmental control of progenitors in organ dysfunction and repairU01HL100402 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI KIM, CARLA F., SCADDEN, DAVID T · 2009 to 2015
$8.5MMUC1-C Oncoprotein Evades Immune Destruction in Non-small Cell Lung CancerR01CA166480 · NCI · DANA-FARBER CANCER INST · PI KUFE, DONALD W., WONG, KWOK KIN · 2012 to 2021
$6.3MTherapeutic strategies for specific subsets of KRAS mutant lung cancersR01CA140594 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI WONG, KWOK KIN · 2009 to 2017
$4.5MLKB1 tumor suppressor and human cancerU01CA141576 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI CASTRILLON, DIEGO H · 2009 to 2013
$4.0MIn vivo analysis of EGFR mutant driven lung cancers responses to radiation therapR01CA122794 · NCI · DANA-FARBER CANCER INST · PI WONG, KWOK KIN · 2006 to 2015
$2.8MIn vivo murine models of metastasis for therapeutic testingR01CA163896 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SHARPLESS, NORMAN E, WONG, KWOK KIN · 2012 to 2016
$2.0MIn Vivo and In Vitro Characterization of Bronchio-Alveolar Stem CellsR01HL090136 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI KIM, CARLA F. · 2007 to 2010
$1.9MMouse Models and Translational Studies of Endometrial CancerR01CA137181 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI CASTRILLON, DIEGO H · 2010 to 2014
$1.8MTargeting MFG-E8 as Melanoma ImmunotherapyR01CA143083 · NCI · DANA-FARBER CANCER INST · PI DRANOFF, GLENN · 2010 to 2014
$1.6MNCI NIH HHS CA098101NCI NIH HHS CA122794NCI NIH HHS CA137181NCI NIH HHS CA140594NCI NIH HHS CA141576NCI NIH HHS CA143083NCI NIH HHS CA163677NCI NIH HHS CA163896NCI NIH HHS CA166480NCI NIH HHS K08 CA163677NCI NIH HHS P01 CA098101NCI NIH HHS P01 CA120964NCI NIH HHS P01 CA154303NCI NIH HHS P0CA120964NCI NIH HHS P0CA154303NCI NIH HHS R01 CA122794NCI NIH HHS R01 CA137181NCI NIH HHS R01 CA140594NCI NIH HHS R01 CA143083NCI NIH HHS R01 CA163896NCI NIH HHS R01 CA166480NCI NIH HHS U01 CA141576NHLBI NIH HHS HL090136NHLBI NIH HHS HL100402NHLBI NIH HHS R01 HL090136NHLBI NIH HHS U01 HL100402
Abstract
Lung squamous cell carcinoma (SCC) is a deadly disease for which current treatments are inadequate. We demonstrate that biallelic inactivation of Lkb1 and Pten in the mouse lung leads to SCC that recapitulates the histology, gene expression, and microenvironment found in human disease. Lkb1;Pten null (LP) tumors expressed the squamous markers KRT5, p63 and SOX2, and transcriptionally resembled the basal subtype of human SCC. In contrast to mouse adenocarcinomas, the LP tumors contained immune populations enriched for tumor-associated neutrophils. SCA1(+)NGFR(+) fractions were enriched for tumor-propagating cells (TPCs) that could serially transplant the disease in orthotopic assays. TPCs in the LP model and NGFR(+) cells in human SCCs highly expressed Pd-ligand-1 (PD-L1), suggesting a mechanism of immune escape for TPCs.
Indexed as
AMP-Activated Protein KinasesAnimalsAntigens, LyB7-H1 AntigenB-LymphocytesCarcinoma, Squamous CellDisease Models, AnimalImmune ToleranceKeratin-15Keratin-5Killer Cells, NaturalLungLung NeoplasmsLymphocyte ActivationMacrophagesMembrane ProteinsAMP-Activated Protein KinasesAntigens, LyB7-H1 AntigenCd274 protein, mouseKeratin-15Keratin-5Krt15 protein, mouseLy6a protein, mouseMembrane ProteinsPhosphoproteinsProtein Serine-Threonine KinasesPTEN PhosphohydrolasePten protein, mouseReceptor, Nerve Growth FactorSox2 protein, mouseSOXB1 Transcription FactorsStk11 protein, mouseTrans-ActivatorsTrp63 protein, mouse
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