ArticleCancer cell2026
Multimodal spatial-omics reveal co-evolution of alveolar progenitors and proinflammatory niches in progression of lung precursor lesions.
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Article in Cancer cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19citing papers in PubMed
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Who cites it
19 citing papers in PubMed.
- The double face of IL-1β in lung cancer.Oncoimmunology · 2026Article
- Unveiling the role of spatial transcriptomics in the analysis of the tumor immune microenvironment (Review).International journal of molecular medicine · 2026Review
- Integrated Multi-Omics Reveals Cellular States and Microenvironmental Remodeling in Coexisting DCIS and IDC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Disulfidptosis: Mechanisms, evidence boundaries, and translational opportunities.Redox biology · 2026Review
- Spatiotemporal lineage tracing reveals the dynamic spatial architecture of tumor growth and metastasis.Nature genetics · 2026Article
- KRAS and TP53 Circulating Tumor DNA are Prognostic in Localized Pancreatic Cancer.Annals of surgical oncology · 2026Article
- Cancer Heterogeneity and Cancer Cell Plasticity: Molecular Mechanisms and Precision Therapy.MedComm · 2026Review
- Article
- [Advances in the Growth Risk Assessment and Precision Management of Pulmonary Subsolid Nodules].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Article
- Macrophages: Targets for next-generation cancer immunotherapy.Cancer cell · 2026Review
- The value of an integrated multi-omics model in the diagnosis of benign and malignant pulmonary nodules.Translational cancer research · 2026Article
- HOXA10 drives immune evasion in early lung adenocarcinoma by recruiting immunosuppressive macrophages via NF-κB/CCL2 signaling.Journal of experimental & clinical cancer research : CR · 2026Article
- Article
- Precancerous microenvironment: A signalling perspective.Current opinion in cell biology · 2026Review
- The promise of IL-1β modulation in NSCLC clinical context.Frontiers in immunology · 2026Article
- Artificial Intelligence-Enabled Multi-Omics for Predicting Immune Checkpoint Inhibitor Response and Resistance.Journal of multidisciplinary healthcare · 2026Review
- The evolving role of the immune microenvironment of tumor draining lymph nodes in the development of biomarkers of non-small cell lung cancer.Frontiers in oncology · 2026Review
- Multicohort Construction, Immune Landscape Analysis, and PCOLCE2 Functional Validation of an Inflammation-Related Prognostic Model in Colorectal Cancer.BioFactors (Oxford, England)Article
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Authors and funding
49 authors.
Fuduan PengDepartment of Genomic Medicine, UT MD Anderson Cancer Center, Houston, TX, USA.
Ansam SinjabDepartment of Translational Molecular Pathology, UT MD Anderson Cancer Center, Houston, TX, USA.
Yibo DaiDepartment of Genomic Medicine, UT MD Anderson Cancer Center, Houston, TX, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA.
Warapen TreekitkarnmongkolDepartment of Translational Molecular Pathology, UT MD Anderson Cancer Center, Houston, TX, USA.
Sujuan YangDepartment of Translational Molecular Pathology, UT MD Anderson Cancer Center, Houston, TX, USA.
Lorena I Gomez BolanosDepartment of Translational Molecular Pathology, UT MD Anderson Cancer Center, Houston, TX, USA.
Tieling ZhouDepartment of Translational Molecular Pathology, UT MD Anderson Cancer Center, Houston, TX, USA.
Minyue ChenDepartment of Translational Molecular Pathology, UT MD Anderson Cancer Center, Houston, TX, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA.
Alejandra G SerranoDepartment of Translational Molecular Pathology, UT MD Anderson Cancer Center, Houston, TX, USA.
Avantika KrishnaThe University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA; Department of Pulmonary Medicine, UT MD Anderson Cancer Center, Houston, TX, USA.
Nastaran KarimiDepartment of Pulmonary Medicine, UT MD Anderson Cancer Center, Houston, TX, USA.
Manvi SharmaDepartment of Translational Molecular Pathology, UT MD Anderson Cancer Center, Houston, TX, USA.
Akshay BasiDepartment of Leukemia, UT MD Anderson Cancer Center, Houston, TX, USA.
Guangsheng PeiDepartment of Genomic Medicine, UT MD Anderson Cancer Center, Houston, TX, USA.
Jianlong LiaoDepartment of Genomic Medicine, UT MD Anderson Cancer Center, Houston, TX, USA.
Yunhe LiuDepartment of Genomic Medicine, UT MD Anderson Cancer Center, Houston, TX, USA.
Jiping FengDepartment of Translational Molecular Pathology, UT MD Anderson Cancer Center, Houston, TX, USA.
Zahraa RahalDepartment of Translational Molecular Pathology, UT MD Anderson Cancer Center, Houston, TX, USA.
Yang LiuDepartment of Genomic Medicine, UT MD Anderson Cancer Center, Houston, TX, USA.
Jiahui JiangDepartment of Genomic Medicine, UT MD Anderson Cancer Center, Houston, TX, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA.
Kai YuDepartment of Genomic Medicine, UT MD Anderson Cancer Center, Houston, TX, USA.
Tala NounDepartment of Translational Molecular Pathology, UT MD Anderson Cancer Center, Houston, TX, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA.
Yuejiang LiuDepartment of Translational Molecular Pathology, UT MD Anderson Cancer Center, Houston, TX, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA.
Khaja KhanDepartment of Translational Molecular Pathology, UT MD Anderson Cancer Center, Houston, TX, USA.
Kyung Serk ChoDepartment of Genomic Medicine, UT MD Anderson Cancer Center, Houston, TX, USA.
Jichao ChenDepartment of Pediatrics, Perinatal Institute Division of Pulmonary Biology, University of Cincinnati and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Luisa M SolisDepartment of Translational Molecular Pathology, UT MD Anderson Cancer Center, Houston, TX, USA.
Sarah MazzilliSection of Computational Biomedicine, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, USA.
Steven DubinettDepartment of Medicine, The University of California, Los Angeles, Los Angeles, CA, USA.
Tina CasconeDepartment of Thoracic Head & Neck Medical Oncology, UT MD Anderson Cancer Center, Houston, TX, USA.
Avrum E SpiraSection of Computational Biomedicine, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, USA; Lung Cancer Initiative at Johnson & Johnson, Boston, MA, USA.
Stephen SwisherDepartment of Cardiovascular and Thoracic Surgery, UT MD Anderson Cancer Center, Houston, TX, USA.
Naoe JimboDepartment of Diagnostic Pathology, Kobe University Hospital, Kobe, Japan.
Takuo HayashiDepartment of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Satsuki KishikawaDepartment of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Kazuya TakamochiDepartment of General Thoracic Surgery, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Tomoo ItohDepartment of Diagnostic Pathology, Kobe University Hospital, Kobe, Japan.
Takashi YaoDepartment of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Kenji SuzukiDepartment of General Thoracic Surgery, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Neda KalhorDepartment of Anatomic Pathology, UT MD Anderson Cancer Center, Houston, TX, USA.
Ignacio I WistubaDepartment of Translational Molecular Pathology, UT MD Anderson Cancer Center, Houston, TX, USA.
Mingyao LiDepartment of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Seyed Javad MoghaddamThe University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA; Department of Pulmonary Medicine, UT MD Anderson Cancer Center, Houston, TX, USA.
Junya FujimotoClinical Research Center, Hiroshima University Hospital, Hiroshima, Japan.
Jared BurksDepartment of Pulmonary Medicine, UT MD Anderson Cancer Center, Houston, TX, USA.
Jeffrey MyersDepartment of Head and Neck Surgery, UT MD Anderson Cancer Center, Houston, TX, USA.
Kadir AkdemirDepartment of Neurosurgery, UT MD Anderson Cancer Center, Houston, TX, USA.
Linghua WangDepartment of Genomic Medicine, UT MD Anderson Cancer Center, Houston, TX, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA; The James P. Allison Institute, UT MD Anderson Cancer Center, Houston, TX, USA; Institute for Data Science in Oncology, UT MD Anderson Cancer Center, Houston, TX, USA. Electronic address: lwang22@mdanderson.org.
Humam KadaraDepartment of Translational Molecular Pathology, UT MD Anderson Cancer Center, Houston, TX, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA; Department of Head and Neck Surgery, UT MD Anderson Cancer Center, Houston, TX, USA. Electronic address: hkadara@mdanderson.org.
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8MCenter for Gastric Pre-Cancer Atlas of Multidimensional Evolution in 3D (GAME3D)U01CA294518 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Paul F Mansfield, Linghua Wang · 2024 to 2026
$5.4MPASSCODE (Pancreatic Adenocarcinoma Stromal Reprograming ConSortium COordination, Data Management and Education)U24CA274274 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI J. Jack LEE, ANIRBAN MAITRA · 2022 to 2026
$4.9MTranscriptional and epigenetic mechanisms of alveologenesis and re-alveologenesisR35HL171346 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI Jichao Chen · 2024 to 2026
$3.3MTumor cell lineage diversity and composition in gastric cancer progression and therapy resistanceR01CA266280 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Pawel K. Mazur, Linghua Wang · 2022 to 2026
$3.2MElucidating the evolution of Krt8+ alveolar cells to Kras-mutant lung preneoplasia and cancerR01CA272863 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Humam Kadara, Seyed Javad Mirhassani Moghaddam · 2022 to 2026
$2.9MInterplay between host microbiome and immunomodulatory responses in the pathogenesis of Kras mutant lung cancerR01CA248731 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KADARA, HUMAM, MOGHADDAM, SEYED JAVAD MIRHASSANI · 2021 to 2025
$2.5MSpatial and temporal tumor-immune co-evolution and interactions that model lung adenocarcinoma developmentU01CA264583 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Humam Kadara, Linghua Wang · 2022 to 2026
$2.1MDissecting the role of B lineage cells in mediating response of resectable lung cancer to neoadjuvant immune-based therapyR01CA287734 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Tina Cascone, Humam Kadara · 2024 to 2026
$2.0MImmunotherapeutic Modalities for K-ras Mutant Lung Cancer: Sex- and Cell Type-Specific Roles of IL-6/STAT3 signalingR01CA225977 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MOGHADDAM, SEYED JAVAD MIRHASSANI · 2018 to 2022
$1.8MSingle Cell Spatial Analysis in TissueR50CA243707 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BURKS, JARED KYLE · 2020 to 2024
$1.3MNovaSeq6000S10OD024977 · OD · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HUFF, VICKI · 2018 to 2018
$995kNCI NIH HHS P30 CA016672NCI NIH HHS R01 CA225977NCI NIH HHS R01 CA248731NCI NIH HHS R01 CA266280NCI NIH HHS R01 CA272863NCI NIH HHS R01 CA287734NCI NIH HHS R50 CA243707NCI NIH HHS U01 CA264583NCI NIH HHS U01 CA294518NCI NIH HHS U24 CA274274NHLBI NIH HHS R35 HL171346NIH HHS S10 OD024977
Abstract
The co-evolution of different cell subsets in the progression of precursor lesions to lung adenocarcinoma (LUAD) is incompletely understood. We generated spatial transcriptomic maps of 56 human precursor lesions and LUADs from 25 patients and of an independent cohort of 36 lesions from 19 patients, analyzing a total of 486,519 spots and 5.4 million cells. We identify region-specific programs that distinguish precursors from LUADs. Spatially resolved clonal architectures reveal patient-specific heterogeneity in evolution of precursors to LUADs. We find epithelial alveolar progenitors expressing tumor-associated meta-programs and residing in niches enriched with proinflammatory subsets including IL1B high macrophages. Epithelial-proinflammatory niches are prevalent in precursor lesions but become less frequent in LUADs. These niches are conserved in mice and promote alveolar progenitor growth. Targeting inflammation alone or in combination with immune checkpoint blockade in precancerous phase reduces alveolar progenitors. Epithelial-inflammatory niches are stage-specific, shape early LUAD development and represent promising targets for interception.
Indexed as
Adenocarcinoma of LungAlveolar Epithelial CellsLung NeoplasmsPrecancerous ConditionsPulmonary AlveoliStem Cell NicheStem CellsAnimalsDisease ProgressionHumansInflammationMiceTranscriptomealveolar progenitorsepithelial-immune nicheIL-1βLUAD interceptionlung adenocarcinomalung precursor lesionsproinflammatory pathwaysreactive type II pneumocytesspatial transcriptomicsXenium in situ
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