Selective elimination of immunosuppressive T cells in patients with multiple myeloma
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...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
17 February 2021
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| In: |
Leukemia
Year: 2021, Jahrgang: 35, Heft: 9, Pages: 2602-2615 |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/s41375-021-01172-x |
| Online-Zugang: | Resolving-System, kostenfrei, Volltext: https://doi.org/10.1038/s41375-021-01172-x Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41375-021-01172-x 
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| Verfasserangaben: | Mohamed H. S. Awwad, Abdelrahman Mahmoud, Heiko Bruns, Hakim Echchannaoui, Katharina Kriegsmann, Raphael Lutz, Marc S. Raab, Uta Bertsch, Markus Munder, Anna Jauch, Katja Weisel, Bettina Maier, Niels Weinhold, Hans Jürgen Salwender, Volker Eckstein, Mathias Hänel, Roland Fenk, Jan Dürig, Benedikt Brors, Axel Benner, Carsten Müller-Tidow, Hartmut Goldschmidt, Michael Hundemer |
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| 245 | 1 | 0 | |a Selective elimination of immunosuppressive T cells in patients with multiple myeloma |c Mohamed H. S. Awwad, Abdelrahman Mahmoud, Heiko Bruns, Hakim Echchannaoui, Katharina Kriegsmann, Raphael Lutz, Marc S. Raab, Uta Bertsch, Markus Munder, Anna Jauch, Katja Weisel, Bettina Maier, Niels Weinhold, Hans Jürgen Salwender, Volker Eckstein, Mathias Hänel, Roland Fenk, Jan Dürig, Benedikt Brors, Axel Benner, Carsten Müller-Tidow, Hartmut Goldschmidt, Michael Hundemer |
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| 520 | |a 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. | ||
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