The pre-existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients.

Humans Multiple Myeloma / drug therapy CD8-Positive T-Lymphocytes Immunotherapy Clone Cells / pathology Antibodies, Bispecific / therapeutic use
BCMA T cell engager T cell exhaustion TCR repertoire bispecific antibodies immunotherapy multiple myeloma single-cell RNA-seq tumor immunology tumor microenvironment

Journal

Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617

Informations de publication

Date de publication:
10 04 2023
Historique:
received: 20 05 2022
revised: 02 11 2022
accepted: 08 02 2023
medline: 12 4 2023
pubmed: 11 3 2023
entrez: 10 3 2023
Statut: ppublish

Résumé

Bispecific T cell engagers (TCEs) have shown promise in the treatment of various cancers, but the immunological mechanism and molecular determinants of primary and acquired resistance to TCEs remain poorly understood. Here, we identify conserved behaviors of bone marrow-residing T cells in multiple myeloma patients undergoing BCMAxCD3 TCE therapy. We show that the immune repertoire reacts to TCE therapy with cell state-dependent clonal expansion and find evidence supporting the coupling of tumor recognition via major histocompatibility complex class I (MHC class I), exhaustion, and clinical response. We find the abundance of exhausted-like CD8

Identifiants

DOI: 10.1016/j.ccell.2023.02.008 PMID: 36898378
pubmed: 36898378
pii: S1535-6108(23)00036-3
doi: 10.1016/j.ccell.2023.02.008
pii:
doi:

Substances chimiques

Antibodies, Bispecific 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

711-725.e6

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. P.N. reports receiving speaker’s bureau honoraria from BMS, Janssen, and Sanofi, and is a consultant/advisory board member for BMS and Janssen. C.M.-T. received research funding from Pfizer and BiolineRX. M.-S.R. reports receiving speaker’s bureau honoraria from Amgen, BMS, Sanofi, and Janssen, and is a consultant/advisory board member for BMS, GSK, Amgen, Janssen, and Pfizer. He received research funding from Amgen, Sanofi, and Janssen. N.J.B. reports receiving speaker’s bureau honoraria from Amgen, BMS, Sanofi, Pfizer, and Janssen, and is a consultant/advisory board member for BMS, Janssen, and Pfizer. All other authors declare no competing interests.

Auteurs

Mirco J Friedrich (MJ)

Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: mfriedri@broadinstitute.org.

Paola Neri (P)

Arnie Charbonneau Cancer Research Institute, University of Calgary, Calgary, Canada; Tom Baker Cancer Center, Department of Hematology and Oncology, Calgary, Canada.

Niklas Kehl (N)

Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Neurology, MCTN, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Julius Michel (J)

Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Neurology, MCTN, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Simon Steiger (S)

Division of Chromatin Networks, BioQuant Center & German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.

Michael Kilian (M)

Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Neurology, MCTN, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Noémie Leblay (N)

Tom Baker Cancer Center, Department of Hematology and Oncology, Calgary, Canada.

Ranjan Maity (R)

Tom Baker Cancer Center, Department of Hematology and Oncology, Calgary, Canada.

Roman Sankowski (R)

Department of Neuropathology, Freiburg University Hospital, Freiburg, Germany.

Holly Lee (H)

Arnie Charbonneau Cancer Research Institute, University of Calgary, Calgary, Canada; Tom Baker Cancer Center, Department of Hematology and Oncology, Calgary, Canada.

Elie Barakat (E)

Tom Baker Cancer Center, Department of Hematology and Oncology, Calgary, Canada.

Sungwoo Ahn (S)

Tom Baker Cancer Center, Department of Hematology and Oncology, Calgary, Canada.

Niels Weinhold (N)

Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.

Karsten Rippe (K)

Division of Chromatin Networks, BioQuant Center & German Cancer Research Center (DKFZ), Heidelberg, Germany.

Lukas Bunse (L)

Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Neurology, MCTN, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Michael Platten (M)

Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Neurology, MCTN, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Helmholtz Institute of Translational Oncology (HI-TRON), Mainz, Germany; National Center for Tumor Diseases (NCT), Heidelberg, Germany; DKFZ Hector Cancer Institute at the University Medical Center Mannheim, Mannheim Germany.

Hartmut Goldschmidt (H)

Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany; National Center for Tumor Diseases (NCT), Heidelberg, Germany.

Carsten Müller-Tidow (C)

Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany; National Center for Tumor Diseases (NCT), Heidelberg, Germany.

Marc-Steffen Raab (MS)

Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany; Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: marc.raab@med.uni-heidelberg.de.

Nizar J Bahlis (NJ)

Arnie Charbonneau Cancer Research Institute, University of Calgary, Calgary, Canada; Tom Baker Cancer Center, Department of Hematology and Oncology, Calgary, Canada. Electronic address: nbahlis@ucalgary.ca.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › The pre-existing T cell landscape determines...
questionsmedicales.fr › Maladies du système immunitaire › Syndromes immunoprolifératifs › Paraprotéinémies › Myélome multiple › The pre-existing T cell landscape determines...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD8+ › The pre-existing T cell landscape determines...
questionsmedicales.fr › Thérapeutique › Biothérapie › Immunothérapie › The pre-existing T cell landscape determines...
questionsmedicales.fr › Cellules › Cellules cultivées › Clones cellulaires › The pre-existing T cell landscape determines...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps bispécifiques › The pre-existing T cell landscape determines...