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ZNF683 marks a CD8+ T cell population associated with anti-tumor immunity following anti-PD-1 therapy for Richter syndrome.
Parry, Erin M; Lemvigh, Camilla K; Deng, Stephanie; Dangle, Nathan; Ruthen, Neil; Knisbacher, Binyamin A; Broséus, Julien; Hergalant, Sébastien; Guièze, Romain; Li, Shuqiang; Zhang, Wandi; Johnson, Connor; Long, Jaclyn M; Yin, Shanye; Werner, Lillian; Anandappa, Annabelle; Purroy, Noelia; Gohil, Satyen; Oliveira, Giacomo; Bachireddy, Pavan; Shukla, Sachet A; Huang, Teddy; Khoury, Joseph D; Thakral, Beenu; Dickinson, Michael; Tam, Constantine; Livak, Kenneth J; Getz, Gad; Neuberg, Donna; Feugier, Pierre; Kharchenko, Peter; Wierda, William; Olsen, Lars Rønn; Jain, Nitin; Wu, Catherine J.
Affiliation
  • Parry EM; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Lemvigh CK; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Health Technology, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
  • Deng S; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Dangle N; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Ruthen N; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Knisbacher BA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Broséus J; Inserm UMRS1256 Nutrition-Génétique et Exposition Aux Risques Environnementaux (N-GERE), Université de Lorraine, 54000 Nancy, France; Université de Lorraine, CHRU-Nancy, Service d'hématologie Biologique, Pôle Laboratoires, 54000 Nancy, France.
  • Hergalant S; Inserm UMRS1256 Nutrition-Génétique et Exposition Aux Risques Environnementaux (N-GERE), Université de Lorraine, 54000 Nancy, France.
  • Guièze R; CHU Clermont-Ferrand, 63000 Clermont-Ferrand, France; EA 7453 (CHELTER), Université Clermont Auvergne, 63001 Clermont-Ferrand, France.
  • Li S; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Translational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Zhang W; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Johnson C; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Long JM; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Division of Gastroen
  • Yin S; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Werner L; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Anandappa A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Purroy N; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Gohil S; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Oliveira G; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA.
  • Bachireddy P; Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Shukla SA; Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Huang T; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Translational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Khoury JD; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
  • Thakral B; Department of Hematopathology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
  • Dickinson M; Peter MacCallum Cancer Centre, Royal Melbourne Hospital, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
  • Tam C; Alfred Health, Melbourne, VIC, Australia; Monash University, Melbourne, VIC, Australia.
  • Livak KJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Translational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Getz G; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Neuberg D; Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Feugier P; Inserm UMRS1256 Nutrition-Génétique et Exposition Aux Risques Environnementaux (N-GERE), Université de Lorraine, 54000 Nancy, France; Université de Lorraine, CHRU Nancy, service d'hématologie clinique, Nancy, France.
  • Kharchenko P; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02215, USA.
  • Wierda W; Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
  • Olsen LR; Department of Health Technology, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
  • Jain N; Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
  • Wu CJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: Catherine_wu@dfci.harvard.edu.
Cancer Cell ; 41(10): 1803-1816.e8, 2023 10 09.
Article in En | MEDLINE | ID: mdl-37738974
ABSTRACT
Unlike many other hematologic malignancies, Richter syndrome (RS), an aggressive B cell lymphoma originating from indolent chronic lymphocytic leukemia, is responsive to PD-1 blockade. To discover the determinants of response, we analyze single-cell transcriptome data generated from 17 bone marrow samples longitudinally collected from 6 patients with RS. Response is associated with intermediate exhausted CD8 effector/effector memory T cells marked by high expression of the transcription factor ZNF683, determined to be evolving from stem-like memory cells and divergent from terminally exhausted cells. This signature overlaps with that of tumor-infiltrating populations from anti-PD-1 responsive solid tumors. ZNF683 is found to directly target key T cell genes (TCF7, LMO2, CD69) and impact pathways of T cell cytotoxicity and activation. Analysis of pre-treatment peripheral blood from 10 independent patients with RS treated with anti-PD-1, as well as patients with solid tumors treated with anti-PD-1, supports an association of ZNF683high T cells with response.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Leukemia, Lymphocytic, Chronic, B-Cell / Lymphoma, Large B-Cell, Diffuse Type of study: Risk_factors_studies Limits: Humans Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2023 Document type: Article Affiliation country:
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Leukemia, Lymphocytic, Chronic, B-Cell / Lymphoma, Large B-Cell, Diffuse Type of study: Risk_factors_studies Limits: Humans Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2023 Document type: Article Affiliation country: