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 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.