Control of PD-L1 expression in CLL-cells by stromal triggering of the Notch-c-Myc-EZH2 oncogenic signaling axis

Böttcher M, Bruns H, Völkl S, Lu J, Chartomatsidou E, Papakonstantinou N, Mentz K, Büttner-Herold M, Zenz T, Herling M, Huber W, Ghia P, Stamatopoulos K, Mackensen A, Mougiakakos D (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Journal for ImmunoTherapy of Cancer BioMed Central

Book Volume: 9

Journal Issue: 4

DOI: 10.1136/jitc-2020-001889

Abstract

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Emerging data suggest that CLL-cells efficiently evade immunosurveillance. T-cell deficiencies in CLL include immuno(metabolic) exhaustion that is achieved by inhibitory molecules, with programmed cell death 1/programmed cell death ligand 1 (PD-L1) signaling emerging as a major underlying mechanism. Moreover, CLL-cells are characterized by a close and recurrent interaction with their stromal niches in the bone marrow and lymph nodes. Here, they receive nurturing signals within a well-protected environment. We could previously show that the interaction of CLL-cells with stroma leads to c-Myc activation that is followed by metabolic adaptations. Recent data indicate that c-Myc also controls expression of the immune checkpoint molecule PD-L1. Therefore, we sought out to determine the role of stromal contact for the CLL-cells' PD-L1 expression and thus their immuno-evasive phenotype.

Authors with CRIS profile

Martin Böttcher Department of Medicine 5 – Haematology and Oncology Heiko Bruns Department of Medicine 5 – Haematology and Oncology Simon Völkl Department of Medicine 5 – Haematology and Oncology Maike Büttner-Herold Medizinische Fakultät Andreas Mackensen Lehrstuhl für Innere Medizin V Dimitrios Mougiakakos Professur für Hämatologie/Onkologie mit dem Schwerpunkt Tumorimmunologie

Involved external institutions

Universitätsspital Zürich (USZ) CH Switzerland (CH) European Molecular Biology Laboratory (EMBL) DE Germany (DE) Ospedale San Raffaele (früher: Centro San Raffaele del Monte Tabor Foundation) IT Italy (IT) Universität zu Köln DE Germany (DE) Centre for Research and Technology Hellas (CERTH) / Ethniko Kentro Erevnas Kai Technologikis Anaptyxis GR Greece (GR)

How to cite

APA:

Böttcher, M., Bruns, H., Völkl, S., Lu, J., Chartomatsidou, E., Papakonstantinou, N.,... Mougiakakos, D. (2021). Control of PD-L1 expression in CLL-cells by stromal triggering of the Notch-c-Myc-EZH2 oncogenic signaling axis. Journal for ImmunoTherapy of Cancer, 9(4). https://doi.org/10.1136/jitc-2020-001889

MLA:

Böttcher, Martin, et al. "Control of PD-L1 expression in CLL-cells by stromal triggering of the Notch-c-Myc-EZH2 oncogenic signaling axis." Journal for ImmunoTherapy of Cancer 9.4 (2021).

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