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Organoid Modeling of the Tumor Immune Microenvironment.
Neal, James T; Li, Xingnan; Zhu, Junjie; Giangarra, Valeria; Grzeskowiak, Caitlin L; Ju, Jihang; Liu, Iris H; Chiou, Shin-Heng; Salahudeen, Ameen A; Smith, Amber R; Deutsch, Brian C; Liao, Lillian; Zemek, Allison J; Zhao, Fan; Karlsson, Kasper; Schultz, Liora M; Metzner, Thomas J; Nadauld, Lincoln D; Tseng, Yuen-Yi; Alkhairy, Sahar; Oh, Coyin; Keskula, Paula; Mendoza-Villanueva, Daniel; De La Vega, Francisco M; Kunz, Pamela L; Liao, Joseph C; Leppert, John T; Sunwoo, John B; Sabatti, Chiara; Boehm, Jesse S; Hahn, William C; Zheng, Grace X Y; Davis, Mark M; Kuo, Calvin J.
Afiliação
  • Neal JT; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
  • Li X; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
  • Zhu J; Department of Electrical Engineering, Stanford University School of Engineering, Stanford, CA, USA.
  • Giangarra V; 10x Genomics, Pleasanton, CA, USA.
  • Grzeskowiak CL; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
  • Ju J; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
  • Liu IH; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
  • Chiou SH; Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA, USA.
  • Salahudeen AA; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
  • Smith AR; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
  • Deutsch BC; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
  • Liao L; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
  • Zemek AJ; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Zhao F; Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA, USA.
  • Karlsson K; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
  • Schultz LM; Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA, USA.
  • Metzner TJ; Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.
  • Nadauld LD; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
  • Tseng YY; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Alkhairy S; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Oh C; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Keskula P; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Mendoza-Villanueva D; TOMA Biosciences, Foster City, CA, USA.
  • De La Vega FM; TOMA Biosciences, Foster City, CA, USA.
  • Kunz PL; Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA, USA.
  • Liao JC; Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.
  • Leppert JT; Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.
  • Sunwoo JB; Department of Otolaryngology, Stanford University School of Medicine, Stanford, CA, USA.
  • Sabatti C; Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA; Department of Statistics, Stanford University School of Humanities and Sciences, Stanford, CA, USA.
  • Boehm JS; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Hahn WC; Broad Institute of Harvard and MIT, Cambridge, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Zheng GXY; 10x Genomics, Pleasanton, CA, USA.
  • Davis MM; Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA, USA; Howard Hughes Medical Institute and Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
  • Kuo CJ; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: cjkuo@stanford.edu.
Cell ; 175(7): 1972-1988.e16, 2018 12 13.
Article em En | MEDLINE | ID: mdl-30550791
ABSTRACT
In vitro cancer cultures, including three-dimensional organoids, typically contain exclusively neoplastic epithelium but require artificial reconstitution to recapitulate the tumor microenvironment (TME). The co-culture of primary tumor epithelia with endogenous, syngeneic tumor-infiltrating lymphocytes (TILs) as a cohesive unit has been particularly elusive. Here, an air-liquid interface (ALI) method propagated patient-derived organoids (PDOs) from >100 human biopsies or mouse tumors in syngeneic immunocompetent hosts as tumor epithelia with native embedded immune cells (T, B, NK, macrophages). Robust droplet-based, single-cell simultaneous determination of gene expression and immune repertoire indicated that PDO TILs accurately preserved the original tumor T cell receptor (TCR) spectrum. Crucially, human and murine PDOs successfully modeled immune checkpoint blockade (ICB) with anti-PD-1- and/or anti-PD-L1 expanding and activating tumor antigen-specific TILs and eliciting tumor cytotoxicity. Organoid-based propagation of primary tumor epithelium en bloc with endogenous immune stroma should enable immuno-oncology investigations within the TME and facilitate personalized immunotherapy testing.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de Antígenos de Linfócitos T / Organoides / Modelos Imunológicos / Microambiente Tumoral / Neoplasias Experimentais Limite: Animals / Female / Humans / Male Idioma: En Revista: Cell Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de Antígenos de Linfócitos T / Organoides / Modelos Imunológicos / Microambiente Tumoral / Neoplasias Experimentais Limite: Animals / Female / Humans / Male Idioma: En Revista: Cell Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos