Selective elimination of immunosuppressive T cells in patients with multiple myeloma

Mohamed H.S. Awwad(Heidelberg University), Abdelrahman Mahmoud(German Cancer Research Center), Heiko Bruns(Universitätsklinikum Erlangen), Hakim Echchannaoui(Johannes Gutenberg University Mainz), Katharina Kriegsmann(Heidelberg University), Raphael Lutz(Heidelberg University), Marc S. Raab(German Cancer Research Center), Uta Bertsch(Heidelberg University), Markus Munder(Johannes Gutenberg University Mainz), Anna Jauch(Heidelberg University), Katja Weisel(Universität Hamburg), Bettina Maier(Heidelberg University), Niels Weinhold(Heidelberg University), Hans Salwender(Asklepios Klinik Altona), Volker Eckstein(Heidelberg University), Mathias Hänel(Klinikum Chemnitz), Roland Fenk(Heinrich Heine University Düsseldorf), Jan Dürig(Essen University Hospital), Benedikt Brors(German Cancer Research Center), Axel Benner(German Cancer Research Center), Carsten Müller‐Tidow(European Molecular Biology Organization), Hartmut Goldschmidt(Heidelberg University), Michael Hundemer(Heidelberg University)
Leukemia
February 17, 2021
10.1038/s41375-021-01172-x
Cited by 57Open Access
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Abstract

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-1 aa26–35*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.

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