ArticleNature genetics2022
Single-nucleus and spatial transcriptome profiling of pancreatic cancer identifies multicellular dynamics associated with neoadjuvant treatment.
Open access · greenAbstract read
In one paragraph
Article in Nature genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 264 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
264citing papers in PubMed, 1 pooled it
36.3field-weighted citation impact, top 1% of its field
What it found
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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
264 citing papers in PubMed, 1 synthesis or guideline pooled it, 377 citations in OpenAlex.
- Metabolic regulation and immunosuppressive functions of lipid-associated macrophages in pancreatic ductal adenocarcinoma.Frontiers in immunology · 2026Pooled it
- Motixafortide, cemiplimab, gemcitabine and nab-paclitaxel in metastatic pancreatic cancer: a single-arm phase 2 study with single-cell correlatives.Nature communications · 2026Trial
- Quemliclustat and chemotherapy with or without zimberelimab in metastatic pancreatic adenocarcinoma: a randomized phase 1 trial.Nature medicine · 2026Trial
- Early Immune Remodeling Steers Clinical Response to First-Line Chemoimmunotherapy in Advanced Gastric Cancer.Cancer discovery · 2024Trial
- Integrative single-cell and spatial transcriptomic approaches to decipher the tumor microenvironment and therapeutic resistance in pancreatic cancer.Cancer biology & therapy · 2026Review
- Clonal lineage tracing and parallel multiomics profiling reveal transcriptional heterogeneity induced by ARID1A deficiency.Science advances · 2026Article
- Tumor cell-intrinsic stress states drive sensitivity to CAR T cell therapy in pancreatic cancer.Science advances · 2026Article
- Asynchronous Evolution of Epithelium and Stroma Differentiates Precursor Lesions from Pancreatic Cancer.Cancer discovery · 2026Article
- 3D multi-omics tumour atlases: from technology to biology and clinical translation.Nature reviews. Cancer · 2026Review
- Targeting Oncomucin-Driven Immunosuppression Improves the Efficacy of K-rasGastroenterology · 2026Article
- Review
- Decoding neuro-tumor interactions in pancreatic cancer: mechanisms, immunosuppressive networks and therapeutic opportunities.Molecular biomedicine · 2026Review
- Clinical Significance of a Cell-Of-Origin-Based Classification in Pancreatic Ductal Adenocarcinoma.Cancer science · 2026Article
- Overcoming cancer resistance in pancreatic cancer: toward dynamic precision oncology.Molecular biology reports · 2026Review
- Article
- Developmental and MAPK-responsive transcription factors regulate distinct malignant cell states and associated genetic dependencies in pancreatic cancer.Nature genetics · 2026Article
- Transcriptome-Based Classification of Resected Pancreatic Ductal Adenocarcinoma Enhances Prognostic Modelling Accuracy of Overall Survival Following Adjuvant Treatment.International journal of cancer · 2026Article
- Review
- Mitophagy-Competent Cancer-Associated Fibroblasts Fuel Chemoresistance by Rewiring Pyrimidine Metabolism in Pancreatic Cancer.Cancer research · 2026Article
- The Metabolic Rheostat Index Uncovers Pathway-Level Coordination, Immunosuppressive Microenvironment Remodeling, and Therapeutic Co-Vulnerabilities in Pancreatic Ductal Adenocarcinoma.Current issues in molecular biology · 2026Article
204 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
65 authors at 7 institutions in 2 countries.
William L Hwang *Center for Systems Biology and Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4514-8837
Karthik A Jagadeesh *Center for Systems Biology and Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Jimmy A Guo *Center for Systems Biology and Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Hannah I Hoffman *Center for Systems Biology and Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Payman YadollahpourCenter for Systems Biology and Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1984-5014
Jason W ReevesNanoString Technologies, Seattle, WA, USA.
Rahul MohanBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Eugene DrokhlyanskyBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Nicholas Van WittenbergheBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Orr AshenbergBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Samouil L FarhiBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-1359-4568
Denis SchapiroBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-9391-5722
Prajan DivakarNanoString Technologies, Seattle, WA, USA.
Eric MillerNanoString Technologies, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-3243-4968
Daniel R ZollingerNanoString Technologies, Seattle, WA, USA.
George EngKoch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Jason M SchenkelKoch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Jennifer SuCenter for Systems Biology and Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Carina ShiauCenter for Systems Biology and Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Patrick YuBroad Institute of MIT and Harvard, Cambridge, MA, USA.
William A Freed-PastorKoch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-7377-2111
Domenic AbbondanzaBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-7202-0225
Arnav MehtaBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Joshua GouldBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9581-5461
Conner LambdenBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Caroline B M PorterBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Alexander TsankovBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Danielle DionneBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Julia WaldmanBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Michael S CuocoBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2163-5120
Lan NguyenBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Toni DeloreyBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6614-3803
Devan PhillipsBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Jaimie L BarthDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Marina KemDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Clifton RodriguesDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Debora CipraniDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Jorge RoldanDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4825-008X
Piotr ZelgaDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1311-7980
Vjola JorgjiDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Jonathan H ChenBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Zackery ElyKoch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Daniel ZhaoNew York Medical College, Valhalla, NY, USA.
Kit FuhrmanNanoString Technologies, Seattle, WA, USA.
Robin FropfNanoString Technologies, Seattle, WA, USA.
Joseph M BeechemNanoString Technologies, Seattle, WA, USA.
Jay S LoefflerCenter for Systems Biology and Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
David P RyanDepartment of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Colin D WeekesDepartment of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Cristina R FerroneDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Motaz QadanDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Martin J AryeeBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-6848-1344
Rakesh K JainCenter for Systems Biology and Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7571-3548
Donna S NeubergDepartment of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2566-3145
Jennifer Y WoCenter for Systems Biology and Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Theodore S HongCenter for Systems Biology and Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Ramnik XavierBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Andrew J AguirreBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Orit Rozenblatt-RosenBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6313-3570
Mari Mino-KenudsonDepartment of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9092-2265
Carlos Fernandez-Del CastilloDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Andrew S LissDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4040-9172
David T TingDepartment of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3261-2322
Tyler JacksKoch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. aviv.regev.sc@gmail.com.ORCID http://orcid.org/0000-0001-5785-8911
Aviv RegevBroad Institute of MIT and Harvard, Cambridge, MA, USA. tjacks@mit.edu.ORCID http://orcid.org/0000-0003-3293-3158
Broad Institute · USHarvard University · USNanostring Technologies (United States) · USMassachusetts Institute of Technology · USBrigham and Women's Hospital · USDana-Farber Cancer Institute · USNew York Medical College · US
Funding
Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Ramnik J Xavier · 1991 to 2026
$35.3MReprogramming PDAC tumor microenvironment to improve immunotherapyU01CA224348 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BOUCHER, YVES, JAIN, RAKESH K. · 2017 to 2021
$2.9MImproving treatment of HER2+ breast cancer brain metastasis by targeting lipid metabolismR01CA259253 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K., VANDER HEIDEN, MATTHEW G. · 2021 to 2025
$2.3MElucidating cancer-intrinsic mechanisms of perineural invasion in pancreatic cancerK08CA270417 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI William L Hwang · 2022 to 2026
$1.6MHoward Hughes Medical InstituteNCI NIH HHS K08 CA270417NCI NIH HHS R01 CA259253NCI NIH HHS U01 CA224348NIDDK NIH HHS P30 DK043351
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and treatment-refractory cancer. Molecular stratification in pancreatic cancer remains rudimentary and does not yet inform clinical management or therapeutic development. Here, we construct a high-resolution molecular landscape of the cellular subtypes and spatial communities that compose PDAC using single-nucleus RNA sequencing and whole-transcriptome digital spatial profiling (DSP) of 43 primary PDAC tumor specimens that either received neoadjuvant therapy or were treatment naive. We uncovered recurrent expression programs across malignant cells and fibroblasts, including a newly identified neural-like progenitor malignant cell program that was enriched after chemotherapy and radiotherapy and associated with poor prognosis in independent cohorts. Integrating spatial and cellular profiles revealed three multicellular communities with distinct contributions from malignant, fibroblast and immune subtypes: classical, squamoid-basaloid and treatment enriched. Our refined molecular and cellular taxonomy can provide a framework for stratification in clinical trials and serve as a roadmap for therapeutic targeting of specific cellular phenotypes and multicellular interactions.
Indexed as
Carcinoma, Pancreatic DuctalPancreatic NeoplasmsBiomarkers, TumorGene Expression ProfilingHumansNeoadjuvant TherapyPrognosisTranscriptomeBiomarkers, Tumor
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