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Selective elimination of immunosuppressive T cells in patients with multiple myeloma
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Selective elimination of immunosuppressive T cells in patients with multiple myeloma
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Journal Article
Selective elimination of immunosuppressive T cells in patients with multiple myeloma
2021
Overview
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.
Highlights
SLAMF7 is a highly expressed marker on the surface of suppressive CD8
+
T cells and its expression correlates with an exhausted phenotype in T cells.
SLAMF7
+
CD8
+
Treg cells could be eliminated using anti-SLAMF7 antibody Elotuzumab via antibody-dependent cellular phagocytosis in vitro and in vivo.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 14/19
/ 38/109
/ 38/77
/ 38/79
/ 64/60
/ Adult
/ Aged
/ Animals
/ Antibodies, Monoclonal, Humanized - therapeutic use
/ Antigens
/ Antineoplastic Agents - therapeutic use
/ Cancer
/ Female
/ Humans
/ Lymphocyte Depletion - methods
/ Male
/ Markers
/ Medicine
/ Mice
/ Multiple Myeloma - immunology
/ Multiple Myeloma - pathology
/ Oncology
/ Patients
/ Signaling Lymphocytic Activation Molecule Family - genetics
/ Signaling Lymphocytic Activation Molecule Family - metabolism
