CD70 reverse signaling enhances NK cell function and immunosurveillance in CD27-expressing B-cell malignancies.

Al Sayed, Mohamad; Ruckstuhl, Carla Alicia; Hilmenyuk, Tamara; Claus, Christina; Bourquin, Jean-Pierre; Bornhauser, Beat C; Radpour, Ramin; Riether, Carsten; Ochsenbein, Adrian (2017). CD70 reverse signaling enhances NK cell function and immunosurveillance in CD27-expressing B-cell malignancies. Blood, 130(3), pp. 297-309. American Society of Hematology 10.1182/blood-2016-12-756585

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The interaction of the tumor necrosis factor receptor (TNFR) CD27 with its ligand CD70 is an emerging target to treat cancer. CD27 signaling provides costimulatory signals to cytotoxic T cells but also increases the frequency of regulatory T cells. Similar to other TNFR ligands, CD70 has been shown to initiate intracellular signaling pathways (CD70 reverse signaling). CD27 is expressed on a majority of B-cell non-Hodgkin lymphoma, but its role in the immune control of lymphoma and leukemia is unknown. We therefore generated a cytoplasmic deletion mutant of CD27 (CD27-trunc) to study the role of CD70 reverse signaling in the immunosurveillance of B-cell malignancies in vivo. Expression of CD27-trunc on malignant cells increased the number of tumor-infiltrating interferon γ-producing natural killer (NK) cells. In contrast, the antitumoral T-cell response remained largely unchanged. CD70 reverse signaling in NK cells was mediated via the AKT signaling pathway and increased NK cell survival and effector function. The improved immune control by activated NK cells prolonged survival of CD27-trunc-expressing lymphoma-bearing mice. Finally, CD70 reverse signaling enhanced survival and effector function of human NK cells in a B-cell acute lymphoblastic leukemia xenotransplants model. Therefore, CD70 reverse signaling in NK cells contributes to the immune control of CD27-expressing B-cell lymphoma and leukemia.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)

UniBE Contributor:

Al Sayed, Mohamad; Ruckstuhl, Carla Alicia; Hilmenyuk, Tamara; Claus, Christina; Radpour, Ramin; Riether, Carsten and Ochsenbein, Adrian

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0006-4971

Publisher:

American Society of Hematology

Language:

English

Submitter:

Nicole Corminboeuf

Date Deposited:

19 Feb 2018 12:15

Last Modified:

21 Jul 2018 02:30

Publisher DOI:

10.1182/blood-2016-12-756585

PubMed ID:

28495792

BORIS DOI:

10.7892/boris.111245

URI:

https://boris.unibe.ch/id/eprint/111245

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