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Single-cell functional genomics reveals determinants of sensitivity and resistance to natural killer cells in blood cancers.
Dufva, Olli; Gandolfi, Sara; Huuhtanen, Jani; Dashevsky, Olga; Duàn, Hanna; Saeed, Khalid; Klievink, Jay; Nygren, Petra; Bouhlal, Jonas; Lahtela, Jenni; Näätänen, Anna; Ghimire, Bishwa R; Hannunen, Tiina; Ellonen, Pekka; Lähteenmäki, Hanna; Rumm, Pauliina; Theodoropoulos, Jason; Laajala, Essi; Härkönen, Jouni; Pölönen, Petri; Heinäniemi, Merja; Hollmén, Maija; Yamano, Shizuka; Shirasaki, Ryosuke; Barbie, David A; Roth, Jennifer A; Romee, Rizwan; Sheffer, Michal; Lähdesmäki, Harri; Lee, Dean A; De Matos Simoes, Ricardo; Kankainen, Matti; Mitsiades, Constantine S; Mustjoki, Satu.
Afiliação
  • Dufva O; Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, 00290 Helsinki, Finland; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland; iCAN Digital Precision Cancer Medicine
  • Gandolfi S; Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, 00290 Helsinki, Finland; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland; iCAN Digital Precision Cancer Medicine
  • Huuhtanen J; Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, 00290 Helsinki, Finland; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland; iCAN Digital Precision Cancer Medicine
  • Dashevsky O; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA; Ludwig Center, Harvard Medical School, Boston, MA 02215, U
  • Duàn H; Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, 00290 Helsinki, Finland; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland; iCAN Digital Precision Cancer Medicine
  • Saeed K; Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, 00290 Helsinki, Finland; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland.
  • Klievink J; Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, 00290 Helsinki, Finland; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland; iCAN Digital Precision Cancer Medicine
  • Nygren P; Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, 00290 Helsinki, Finland; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland; iCAN Digital Precision Cancer Medicine
  • Bouhlal J; Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, 00290 Helsinki, Finland; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland; iCAN Digital Precision Cancer Medicine
  • Lahtela J; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, 00014 Helsinki, Finland.
  • Näätänen A; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, 00014 Helsinki, Finland.
  • Ghimire BR; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, 00014 Helsinki, Finland.
  • Hannunen T; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, 00014 Helsinki, Finland.
  • Ellonen P; Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, 00014 Helsinki, Finland.
  • Lähteenmäki H; Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, 00290 Helsinki, Finland; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland.
  • Rumm P; Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, 00290 Helsinki, Finland; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland.
  • Theodoropoulos J; Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, 00290 Helsinki, Finland; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland.
  • Laajala E; Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, 00290 Helsinki, Finland; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland; iCAN Digital Precision Cancer Medicine
  • Härkönen J; Faculty of Health Sciences, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
  • Pölönen P; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Heinäniemi M; Faculty of Health Sciences, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
  • Hollmén M; Medicity Research Laboratory, University of Turku, 20014 Turku, Finland.
  • Yamano S; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA; Ludwig Center, Harvard Medical School, Boston, MA 02215, U
  • Shirasaki R; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA; Ludwig Center, Harvard Medical School, Boston, MA 02215, U
  • Barbie DA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA; Ludwig Center, Harvard Medical School, Boston, MA 02215, U
  • Roth JA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Romee R; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA; Ludwig Center, Harvard Medical School, Boston, MA 02215, USA.
  • Sheffer M; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA; Ludwig Center, Harvard Medical School, Boston, MA 02215, U
  • Lähdesmäki H; Department of Computer Science, Aalto University, 02150 Espoo, Finland.
  • Lee DA; Hematology/Oncology/BMT, Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, Columbus, OH 43205, USA.
  • De Matos Simoes R; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA; Ludwig Center, Harvard Medical School, Boston, MA 02215, U
  • Kankainen M; Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, 00290 Helsinki, Finland; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland; iCAN Digital Precision Cancer Medicine
  • Mitsiades CS; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA; Ludwig Center, Harvard Medical School, Boston, MA 02215, U
  • Mustjoki S; Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, 00290 Helsinki, Finland; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland; iCAN Digital Precision Cancer Medicine
Immunity ; 56(12): 2816-2835.e13, 2023 Dec 12.
Article em En | MEDLINE | ID: mdl-38091953
ABSTRACT
Cancer cells can evade natural killer (NK) cell activity, thereby limiting anti-tumor immunity. To reveal genetic determinants of susceptibility to NK cell activity, we examined interacting NK cells and blood cancer cells using single-cell and genome-scale functional genomics screens. Interaction of NK and cancer cells induced distinct activation and type I interferon (IFN) states in both cell types depending on the cancer cell lineage and molecular phenotype, ranging from more sensitive myeloid to less sensitive B-lymphoid cancers. CRISPR screens in cancer cells uncovered genes regulating sensitivity and resistance to NK cell-mediated killing, including adhesion-related glycoproteins, protein fucosylation genes, and transcriptional regulators, in addition to confirming the importance of antigen presentation and death receptor signaling pathways. CRISPR screens with a single-cell transcriptomic readout provided insight into underlying mechanisms, including regulation of IFN-γ signaling in cancer cells and NK cell activation states. Our findings highlight the diversity of mechanisms influencing NK cell susceptibility across different cancers and provide a resource for NK cell-based therapies.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Hematológicas / Neoplasias Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Hematológicas / Neoplasias Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article