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A human lymphoma organoid model for evaluating and targeting the follicular lymphoma tumor immune microenvironment.
Kastenschmidt, Jenna M; Schroers-Martin, Joseph G; Sworder, Brian J; Sureshchandra, Suhas; Khodadoust, Michael S; Liu, Chih Long; Olsen, Mari; Kurtz, David M; Diehn, Maximilian; Wagar, Lisa E; Alizadeh, Ash A.
Afiliación
  • Kastenschmidt JM; Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA 92617, USA; Institute for Immunology, University of California, Irvine, Irvine, CA 92617, USA; Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA 92617, USA; Cancer Research Ins
  • Schroers-Martin JG; Division of Oncology, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
  • Sworder BJ; Division of Oncology, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
  • Sureshchandra S; Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA 92617, USA; Institute for Immunology, University of California, Irvine, Irvine, CA 92617, USA; Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA 92617, USA; Cancer Research Ins
  • Khodadoust MS; Division of Oncology, Department of Medicine, Stanford University, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University, Stanford, CA 94305, USA.
  • Liu CL; Division of Oncology, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
  • Olsen M; Division of Oncology, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
  • Kurtz DM; Division of Oncology, Department of Medicine, Stanford University, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University, Stanford, CA 94305, USA.
  • Diehn M; Stanford Cancer Institute, Stanford University, Stanford, CA 94305, USA; Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305, USA.
  • Wagar LE; Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA 92617, USA; Institute for Immunology, University of California, Irvine, Irvine, CA 92617, USA; Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA 92617, USA; Cancer Research Ins
  • Alizadeh AA; Division of Oncology, Department of Medicine, Stanford University, Stanford, CA 94305, USA; Division of Hematology, Department of Medicine, Stanford University, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regen
Cell Stem Cell ; 31(3): 410-420.e4, 2024 03 07.
Article en En | MEDLINE | ID: mdl-38402619
ABSTRACT
Heterogeneity in the tumor microenvironment (TME) of follicular lymphomas (FLs) can affect clinical outcomes. Current immunotherapeutic strategies, including antibody- and cell-based therapies, variably overcome pro-tumorigenic mechanisms for sustained disease control. Modeling the intact FL TME, with its native, syngeneic tumor-infiltrating leukocytes, is a major challenge. Here, we describe an organoid culture method for cultivating patient-derived lymphoma organoids (PDLOs), which include cells from the native FL TME. We define the robustness of this method by successfully culturing cryopreserved FL specimens from diverse patients and demonstrate the stability of TME cellular composition, tumor somatic mutations, gene expression profiles, and B/T cell receptor dynamics over 3 weeks. PDLOs treated with CD3CD19 and CD3CD20 therapeutic bispecific antibodies showed B cell killing and T cell activation. This stable system offers a robust platform for advancing precision medicine efforts in FL through patient-specific modeling, high-throughput screening, TME signature identification, and treatment response evaluation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfoma Folicular Límite: Humans Idioma: En Revista: Cell Stem Cell Año: 2024 Tipo del documento: Article
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfoma Folicular Límite: Humans Idioma: En Revista: Cell Stem Cell Año: 2024 Tipo del documento: Article