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Scheuerpflug, A.C. ; Ahmetlic, F. ; Bauer, V. ; Riedel, T. ; Röcken, M.* ; Mocikat, R.

The role of dendritic cells for therapy of B-cell lymphoma with immune checkpoint inhibitors.

Cancer Immunol. Immunother. 70, 1343–1350 (2021)
Verlagsversion Postprint Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Immune checkpoint blocking (ICB) is a promising new tool of cancer treatment. Yet, the underlying therapeutic mechanisms are not fully understood. Here we investigated the role of dendritic cells (DCs) for the therapeutic effect of ICB in a lambda-MYC-transgenic mouse model of endogenously arising B-cell lymphoma. The growth of these tumors can be effectively delayed by antibodies against CTLA-4 and PD-1. Tumor-infiltrating DCs from mice having received therapy showed an upregulation of costimulatory molecules as well as an augmented IL-12/IL-10 ratio as compared to untreated controls. Both alterations seemed to be induced by interferon-gamma (IFN-gamma), which is upregulated in T cells and natural killer cells upon ICB. Furthermore, the enhanced IL-12/IL-10 ratio, which favors Th1-prone antitumor T-cell responses, was a consequence of direct interaction of ICB antibodies with DCs. Importantly, the capability of tumor-infiltrating DCs of stimulating peptide-specific or allogeneic T-cell responses in vitro was improved when DCs were derived from ICB-treated mice. The data indicate that ICB therapy is not only effective by directly activating T cells, but also by triggering a complex network, in which DCs play a pivotal role at the interface between innate and adaptive antitumor responses.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Immune Checkpoint Blocking ; Lymphoma ; Tumor-infiltrating Dendritic Cells ; Interferon-γ ; λ ; -myc Mouse; Natural-killer-cells; Costimulatory Molecules; Pd-1 Blockade; Receptor; Expression; Cancer; Activation; Rejection; Pathway; Ctla-4
ISSN (print) / ISBN 0340-7004
e-ISSN 1432-0851
Zeitschrift Cancer Immunology, Immunotherapy
Quellenangaben Band: 70, Heft: , Seiten: 1343–1350 Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort One New York Plaza, Suite 4600, New York, Ny, United States
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) AG Translationale Molekulare Immunologie (TMI)
Institute of Molecular Immunology (IMI)
Förderungen Deutsche Forschungsgemeinschaft
Wilhelm-Sander-Stiftung
Deutsche Krebshilfe
Projekt DEAL