Selective elimination of immunosuppressive T cells in patients with multiple myeloma

Awwad MHS, Mahmoud A, Bruns H, Echchannaoui H, Kriegsmann K, Lutz R, Raab MS, Bertsch U, Munder M, Jauch A, Weisel K, Maier B, Weinhold N, Salwender HJ, Eckstein V, Haenel M, Fenk R, Duerig J, Brors B, Benner A, Mueller-Tidow C, Goldschmidt H, Hundemer M (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Leukemia Springer Nature

DOI: 10.1038/s41375-021-01172-x

Abstract

Elimination of suppressive T cells may enable and enhance cancer immunotherapy. Here, we demonstrate that the cell membrane protein SLAMF7 was highly expressed on immunosuppressive CD8+CD28-CD57+ Tregs in multiple myeloma (MM). SLAMF7 expression associated with T cell exhaustion surface markers and exhaustion-related transcription factor signatures. T cells from patients with a high frequency of SLAMF7+CD8+ T cells exhibited decreased immunoreactivity towards the MART-1aa26–35*A27L antigen. A monoclonal anti-SLAMF7 antibody (elotuzumab) specifically depleted SLAMF7+CD8+ T cells in vitro and in vivo via macrophage-mediated antibody-dependent cellular phagocytosis (ADCP). Anti-SLAMF7 treatment of MM patients depleted suppressive T cells in peripheral blood. These data highlight SLAMF7 as a marker for suppressive CD8+ Treg and suggest that anti-SLAMF7 antibodies can be used to boost anti-tumoral immune responses in cancer patients.

Authors with CRIS profile

Heiko Bruns Department of Medicine 5 – Haematology and Oncology

Involved external institutions

Universitätsklinikum Heidelberg DE Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Johannes Gutenberg-Universität Mainz (JGU) DE Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Asklepios Klinik Altona DE Germany (DE) Klinikum Chemnitz DE Germany (DE) Heinrich-Heine-Universität Düsseldorf DE Germany (DE) Universitätsklinikum Essen DE Germany (DE)

How to cite

APA:

Awwad, M.H.S., Mahmoud, A., Bruns, H., Echchannaoui, H., Kriegsmann, K., Lutz, R.,... Hundemer, M. (2021). Selective elimination of immunosuppressive T cells in patients with multiple myeloma. Leukemia. https://doi.org/10.1038/s41375-021-01172-x

MLA:

Awwad, Mohamed H. S., et al. "Selective elimination of immunosuppressive T cells in patients with multiple myeloma." Leukemia (2021).

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