ArticleNature medicine2023
Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma.
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Article in Nature medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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58citing papers in PubMed
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Who cites it
58 citing papers in PubMed, 77 citations in OpenAlex.
- An AI-integrated organoid platform enables high-throughput functional evaluation of bioactive metal ions.Bioactive materials · 2026Article
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- Stromal and endothelial transcriptional changes during progression from MGUS to myeloma and after treatment response.Nature communications · 2026Article
- SSTNSignal transduction and targeted therapy · 2026Article
- Single-cell multiomics reveals regulatory mechanisms of CAR T-cell persistence and dysfunction in multiple myeloma.Blood neoplasia · 2026Article
- A TRPM4-associated necrotic cell death signature for prognostic stratification in pancreatic cancer.Journal of gastrointestinal oncology · 2026Article
- Genetically driven immune microenvironment states associate with therapeutic responses in MYD88 mutant lymphomas.Molecular cancer · 2026Article
- Comparative Molecular Insights and Computational Modeling of Multiple Myeloma and Osteosarcoma.International journal of molecular sciences · 2026Review
- Valrubicin-loaded immunoliposomes targeting antigens on immunosuppressive cells to circumvent resistance to cancer immunotherapy.Cell reports. Medicine · 2026Article
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- comBO: A combined human bone and lympho-myeloid bone marrow organoid for preclinical modeling of hematopoietic disorders.Cell stem cell · 2026Article
- Immune heterogeneity at diagnosis influences treatment response and survival in multiple myeloma.Discover oncology · 2026Article
- Integrated RNA-seq and RT-qPCR Workflow Identifies Non-IGH Fusion Transcripts as Individualized Molecular Markers for Monitoring Multiple Myeloma.Biomedicines · 2026Article
- Mezigdomide combined with bortezomib disrupts the cell cycle and elicits superior antitumor effects in multiple myeloma.Blood neoplasia · 2026Article
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- Differential expression of immune activation markers in T cells from patients with multiple myeloma.Frontiers in oncology · 2026Article
- Immunologic Combinations in Multiple Myeloma: Synergistic Stimulation with T cells and NK cells.International journal of biological sciences · 2026Review
- Precision radiolabeled B-cell maturation nanobody for targeted PET imaging and radioligand therapy of disseminated multiple myeloma.Theranostics · 2026Article
- Hybrid Nanocarriers for Cancer Therapy: Advancements in Co-Delivery of Gene Therapy and Immunotherapy.International journal of molecular sciences · 2025Review
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Authors and funding
46 authors at 13 institutions in 6 countries.
Marta LarrayozDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, Cancer Center University of Navarra (CCUN), Navarra Institute for Health Research (IDISNA), CIBERONC, Pamplona, Spain.ORCID http://orcid.org/0000-0001-6097-8244
Maria J Garcia-BarchinoDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, Cancer Center University of Navarra (CCUN), Navarra Institute for Health Research (IDISNA), CIBERONC, Pamplona, Spain.
Jon CelayDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, Cancer Center University of Navarra (CCUN), Navarra Institute for Health Research (IDISNA), CIBERONC, Pamplona, Spain.ORCID http://orcid.org/0000-0002-2017-4206
Amaia EtxebesteDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, Cancer Center University of Navarra (CCUN), Navarra Institute for Health Research (IDISNA), CIBERONC, Pamplona, Spain.ORCID http://orcid.org/0000-0003-4408-0981
Maddalen JimenezDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, Cancer Center University of Navarra (CCUN), Navarra Institute for Health Research (IDISNA), CIBERONC, Pamplona, Spain.
Cristina PerezDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, Cancer Center University of Navarra (CCUN), Navarra Institute for Health Research (IDISNA), CIBERONC, Pamplona, Spain.
Raquel OrdoñezDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, Cancer Center University of Navarra (CCUN), Navarra Institute for Health Research (IDISNA), CIBERONC, Pamplona, Spain.
Cesar CobaledaImmune System Development and Function Unit, Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas/Universidad Autonoma, Madrid, Spain.ORCID http://orcid.org/0000-0003-3807-9204
Cirino BottaDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, Cancer Center University of Navarra (CCUN), Navarra Institute for Health Research (IDISNA), CIBERONC, Pamplona, Spain.
Vicente FresquetDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, Cancer Center University of Navarra (CCUN), Navarra Institute for Health Research (IDISNA), CIBERONC, Pamplona, Spain.ORCID http://orcid.org/0000-0003-1511-8354
Sergio RoaDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, Cancer Center University of Navarra (CCUN), Navarra Institute for Health Research (IDISNA), CIBERONC, Pamplona, Spain.ORCID http://orcid.org/0000-0003-1095-0715
Ibai GoicoecheaDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, Cancer Center University of Navarra (CCUN), Navarra Institute for Health Research (IDISNA), CIBERONC, Pamplona, Spain.ORCID http://orcid.org/0000-0002-5329-2225
Catarina MaiaDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, Cancer Center University of Navarra (CCUN), Navarra Institute for Health Research (IDISNA), CIBERONC, Pamplona, Spain.
Miren LasagaDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, Cancer Center University of Navarra (CCUN), Navarra Institute for Health Research (IDISNA), CIBERONC, Pamplona, Spain.
Marta ChesiDepartment of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA.ORCID http://orcid.org/0000-0002-4024-8225
P Leif BergsagelDepartment of Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA.ORCID http://orcid.org/0000-0003-1523-7388
Maria J LarrayozDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, Cancer Center University of Navarra (CCUN), Navarra Institute for Health Research (IDISNA), CIBERONC, Pamplona, Spain.
Maria J CalasanzDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, Cancer Center University of Navarra (CCUN), Navarra Institute for Health Research (IDISNA), CIBERONC, Pamplona, Spain.ORCID http://orcid.org/0000-0002-0374-3008
Elena Campos-SanchezImmune System Development and Function Unit, Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas/Universidad Autonoma, Madrid, Spain.
Jorge Martinez-CanoImmune System Development and Function Unit, Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas/Universidad Autonoma, Madrid, Spain.ORCID http://orcid.org/0000-0001-6809-5489
Carlos PanizoDepartment of Hematology, Clinica Universidad de Navarra, CCUN, IDISNA, CIBERONC, Pamplona, Spain.
Paula Rodriguez-OteroDepartment of Hematology, Clinica Universidad de Navarra, CCUN, IDISNA, CIBERONC, Pamplona, Spain.
Silvestre VicentProgram in Solid Tumors, Center for Applied Medical Research CIMA, University of Navarra, IDISNA, CIBERONC, Pamplona, Spain.ORCID http://orcid.org/0000-0002-9457-6881
Giovanna RoncadorMonoclonal Antibodies Unit, Biotechnology Program, Spanish National Cancer Research Centre CNIO, Madrid, Spain.
Patricia GonzalezMonoclonal Antibodies Unit, Biotechnology Program, Spanish National Cancer Research Centre CNIO, Madrid, Spain.
Satoru TakahashiDepartment of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.ORCID http://orcid.org/0000-0002-8540-7760
Samuel G KatzDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.
Loren D WalenskyDepartment of Pediatric Oncology and Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Shannon M RuppertOncology Biomarker Development, Genentech, South San Francisco, CA, USA.
Elisabeth A LasaterDepartment of Translational Oncology, Genentech, South San Francisco, CA, USA.
Maria AmannRoche Innovation Center Zurich, Roche Pharmaceutical Research and Early Development (pRED), Schlieren, Switzerland.
Teresa LozanoProgram of Immunology and Immunotherapy, Center for Applied Medical Research CIMA, University of Navarra, IDISNA, CIBEREHD, Pamplona, Spain.
Diana LlopizProgram of Immunology and Immunotherapy, Center for Applied Medical Research CIMA, University of Navarra, IDISNA, CIBEREHD, Pamplona, Spain.
Pablo SarobeProgram of Immunology and Immunotherapy, Center for Applied Medical Research CIMA, University of Navarra, IDISNA, CIBEREHD, Pamplona, Spain.
Juan J LasarteProgram of Immunology and Immunotherapy, Center for Applied Medical Research CIMA, University of Navarra, IDISNA, CIBEREHD, Pamplona, Spain.ORCID http://orcid.org/0000-0003-1641-3881
Nuria PlanellTranslational Bioinformatics Unit, Navarra-Biomed, Public University of Navarra, IDISNA, Pamplona, Spain.
David Gomez-CabreroTranslational Bioinformatics Unit, Navarra-Biomed, Public University of Navarra, IDISNA, Pamplona, Spain.
Olga KudryashovaBostonGene, Waltham, MA, USA.ORCID http://orcid.org/0000-0003-3320-7764
Anna KurilovichBostonGene, Waltham, MA, USA.ORCID http://orcid.org/0000-0002-3952-8609
Maria V RevueltaDepartment of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-7922-0713
Leandro CerchiettiDepartment of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0003-0608-1350
Xabier AgirreDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, Cancer Center University of Navarra (CCUN), Navarra Institute for Health Research (IDISNA), CIBERONC, Pamplona, Spain.ORCID http://orcid.org/0000-0002-6558-9560
Jesus San MiguelDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, Cancer Center University of Navarra (CCUN), Navarra Institute for Health Research (IDISNA), CIBERONC, Pamplona, Spain.ORCID http://orcid.org/0000-0002-9183-4857
Bruno PaivaDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, Cancer Center University of Navarra (CCUN), Navarra Institute for Health Research (IDISNA), CIBERONC, Pamplona, Spain.ORCID http://orcid.org/0000-0003-1977-3815
Felipe ProsperDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, Cancer Center University of Navarra (CCUN), Navarra Institute for Health Research (IDISNA), CIBERONC, Pamplona, Spain.ORCID http://orcid.org/0000-0001-6115-8790
Jose A Martinez-ClimentDivision of Hemato-Oncology, Center for Applied Medical Research CIMA, Cancer Center University of Navarra (CCUN), Navarra Institute for Health Research (IDISNA), CIBERONC, Pamplona, Spain. jamcliment@unav.es.ORCID http://orcid.org/0000-0002-7938-3950
Centro de Investigación Biomédica en Red de Cáncer · ESClinica Universidad de Navarra · ESCentro de Investigación Biomédica en Red · ESConsejo Superior de Investigaciones Científicas · ESAddgene · USCornell University · USMayo Clinic in Arizona · USNavarrabiomed · ESSpanish National Cancer Research Centre · ESHarvard University · USRoche (Switzerland) · CHUniversity of Tsukuba · JPYale University · US
Funding
Project 4: Targeting Resistance to T-Cell Directed Therapy in Multiple MyelomaP50CA186781 · NCI · MAYO CLINIC ARIZONA · PI Rafael Fonseca · 2015 to 2026
$25.5MDissecting and Targeting Deregulated Mitochondrial Apoptosis in Human CancerR35CA197583 · NCI · DANA-FARBER CANCER INST · PI Loren David Walensky · 2015 to 2026
$12.5MRole of the stromal microenvironment in B-cell lymphoma progression and immune escapeR01CA242069 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI CERCHIETTI, LEANDRO C · 2020 to 2024
$2.9Mpreclinical optimization of BCMA directed T cell therapyR01CA272426 · NCI · MAYO CLINIC ARIZONA · PI Peter Leif Bergsagel, Marta Chesi · 2023 to 2026
$2.5MCredentialing a Genetically Engineered Clinically-Relevant Mouse Model of Multiple MyelomaR01CA234181 · NCI · MAYO CLINIC ARIZONA · PI CHESI, MARTA · 2019 to 2023
$1.9MNCI NIH HHS P50 CA186781NCI NIH HHS R01 CA234181NCI NIH HHS R01 CA242069NCI NIH HHS R01 CA272426NCI NIH HHS R35 CA197583
Abstract
The historical lack of preclinical models reflecting the genetic heterogeneity of multiple myeloma (MM) hampers the advance of therapeutic discoveries. To circumvent this limitation, we screened mice engineered to carry eight MM lesions (NF-κB, KRAS, MYC, TP53, BCL2, cyclin D1, MMSET/NSD2 and c-MAF) combinatorially activated in B lymphocytes following T cell-driven immunization. Fifteen genetically diverse models developed bone marrow (BM) tumors fulfilling MM pathogenesis. Integrative analyses of ∼500 mice and ∼1,000 patients revealed a common MAPK-MYC genetic pathway that accelerated time to progression from precursor states across genetically heterogeneous MM. MYC-dependent time to progression conditioned immune evasion mechanisms that remodeled the BM microenvironment differently. Rapid MYC-driven progressors exhibited a high number of activated/exhausted CD8
Indexed as
Multiple MyelomaAnimalsCD8-Positive T-LymphocytesImmune EvasionImmunotherapyMiceT-Lymphocytes, RegulatoryTumor Microenvironment
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