Selective elimination of immunosuppressive T cells in patients with multiple myeloma.

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: 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
• Journal: Leukemia (Leukemia) Vol. 35 Issue 9 Pg. 2602-2615 (09 2021) ISSN: 1476-5551 [Electronic] England
• PMID: 33597728 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• SLAMF7 protein, human
• Signaling Lymphocytic Activation Molecule Family
• elotuzumab

Topics

• Adult
• Aged
• Animals
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Apoptosis
• Cell Proliferation
• Female
• Humans
• Lymphocyte Depletion (methods)
• Male
• Mice
• Mice, Inbred NOD
• Mice, SCID
• Middle Aged
• Multiple Myeloma (immunology, pathology, therapy)
• Prognosis
• Signaling Lymphocytic Activation Molecule Family (genetics, metabolism)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays