Furthermore, we identified elevated expression of immune checkpoints, such as PD-1 on CD8+ T cells and KLRC1 (NKG2A) on CD16- NK cells.<h4>Significance</h4>This study characterizes the TME in EMM lesions and paired BM from patients with multiple myeloma, revealing a high proportion of less cytotoxic CD16- NK cells in EMM tumors and suggesting that direct cell-cell interactions may underlie the CD8+ T-cell exhaustion observed in a subset of these tumors. Here, CD8A is linked to plasma cell myeloma.