Immunosuppressive monocyte/macrophages inhibit NK-cell activation and killing via the PD-1/PD-L1 axis. (A) Fluorescence-activated cell sorter histogram showing unsorted (gray) and KHYG1 PD-1^hi sorted (clear) NK cells. (B) Histograms show killing and CD107a degranulation of KHYG-1 PD-1^hi/lo cells against K562 and HDLM2 targets with/without PD-1 blockade. (C) M-CSF and interleukin 6 M6 cultured PD-L1-enriched monocytes were co-incubated with KHYG1 PD-1^hi cells with PD-1 blockade (middle) or isotype alone (left). CD137 was quantified on NK cells on exposure to the PD-L1 nonexpressing line SU-DHL-4 cell-line. In the control assay, KHYG1 PD-1^hi cells were co-incubated with SU-DHL-4 targets alone (right). (D) Target cell lysis by primary NK cells from patients with cHL (n = 3) on exposure to the PD-L1 expressing cell-line HDLM2. (E) Rituximab-mediated ADCC target cell lysis by primary NK cells from patients with DLBCL (n = 3) against the PD-L1 expressing cell-line TK in the presence of pembrolizumab. In the control assays, target cells and primary NK cells were co-incubated with immunoglobulin G4 isotype control. ADCC, antibody dependent cellular cytotoxicity.