ZNF683 marks a CD8 + T cell population associated with anti-tumor immunity following anti-PD-1 therapy for Richter syndrome.

Autor: 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 Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA., 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.
Jazyk: angličtina
Zdroj: Cancer cell [Cancer Cell] 2023 Oct 09; Vol. 41 (10), pp. 1803-1816.e8. Date of Electronic Publication: 2023 Sep 21.
DOI: 10.1016/j.ccell.2023.08.013
Abstrakt: 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 ZNF683 high T cells with response.
Competing Interests: Declaration of interests C.J.W. receives funding support from: Pharmacyclics; holds equity in: BioNTech, Inc; G.G. is a founder, consultant and holds privately held equity in Scorpion Therapeutics, receives funding support from: IBM and Pharmacyclics, is an inventor on patent applications related to: MuTect, ABSOLUTE, MutSig, MSMuTect, MSMutSig, MSIDetect, POLYSOLVER, and TensorQTL; R.G. receives funding support from: Abbvie, Janssen, Gilead, AstraZeneca, and Roche; N.J. receives research funding from: Pharmacyclics, AbbVie, Genentech, AstraZeneca, BMS, Pfizer, Servier, ADC Therapeutics, Cellectis, Precision BioSciences, Adaptive Biotechnologies, Incyte, Aprea Therapeutics, Fate Therapeutics, Mingsight, Takeda, Medisix, Loxo Oncology, Novalgen and serves on Advisory Board/Honoraria: Pharmacyclics, Janssen, AbbVie, Genentech, AstraZeneca, BMS, Adaptive Biotechnologies, Precision BioSciences, Servier, Beigene, Cellectis, TG Therapeutics, ADC Therapeutics, MEI Pharma; W.G.W. reports funding from GSK/Novartis, Abbvie, Genentech, Pharmacyclics LLC, AstraZeneca/Acerta Pharma, Gilead Sciences, Juno Therapeutics, KITE Pharma, Sunesis, Miragen, Oncternal Therapeutics, Inc., Cyclacel, Loxo Oncology, Inc., Janssen, Xencor. B.A.K., C.J.W. and G.G. are inventors on patent: “Compositions, panels, and methods for characterizing chronic lymphocytic leukemia” (PCT/US21/45144); S.A.S. reports nonfinancial support from Bristol-Myers Squibb, and equity in Agenus Inc., Agios Pharmaceuticals, Breakbio Corp., Bristol-Myers Squibb and Lumos Pharma. N.P. is currently an employee of Bristol Myers Squibb. K.J.L. holds equity in Standard BioTools Inc. (formerly Fluidigm Corporation). C.J.W. and E.M.P are inventors on a patent, US Utility Application No. US-2022-0298580-A1 filed on 02/10/2022, International Application No. WO/2021/041669 filed on 9/15/2022, “Immune Signatures Predictive of Response to PD-1 Blockade in Richter’s transformation.” M.D., J.D.K. and B.T. have no relevant conflict of interest. C.T. reports honorarium from Beigene, Janssen, Abbvie, AZ and LOXO and research funding from Beigene, Janssen, and AbbVie.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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