SHP-1-mediated inhibitory signals promote responsiveness and anti-tumour functions of natural killer cells. We then assessed the anti-tumor efficacy of monalizumab in co-cultures of NK cells with tumor cell lines with different levels of HLA-E expression ( Figure S6).

We know that our products are good, and we want you to be happy with your purchase for the rest of your life. As expected, the frequency of activated NKG2A + NK cells—assessed based on the expression of CD107a, a degranulation marker—was higher in cocultures with Qa-1 b-deficient A20 cells than in cocultures with parental cells (data not shown).NK cells were incubated at a ratio of 1:1 or 5:2 with target cell lines (SCCHN, ovarian cancer cell lines or K562 cells transfected to express HLA-E and/or PDL-1).

We then sought to assess the blocking activity of monalizumab on effector cells by monitoring the cell surface expression of CD107 by NKG2A + NK cells cocultured with K562 tumor target cells expressing HLA-E ( Figures 5A and 5B). F) The CD8 + T cells generated in (E) were co-cultured with Flu peptide-pulsed K562 cells expressing PD-L1, HLA-E and HLA-A2 without (control) or with monalizumab (mona), durvalumab (durva), or both antibodies (combo). We confirmed that the blockade of NKG2A in vitro promoted the expression of CD107a by NK cells cocultured with Qa-1B + A20 tumors, but not with Qa-1B − YAC-1 target cells ( Figure S1B).The frequency of NKG2A + NK cells in the tumor was higher than that in the spleen, but tumor-infiltrating NK cells did not express PD-1, as observed in the A20 model ( Figure 3A). By contrast, the use of anti-NKG2A and anti-PD-L1 mAbs in combination increased the frequency of CD107a-expressing NKG2A + PD-1 + CD8 + TILs. Nevertheless, unlike PD-1 expression, which can be observed on the surface of CD8 + T cells from whole blood or lymph nodes from cancer patients, the number of NKG2A-expressing CD8 + T cells was selectively increased at the tumor bed or adjacent tissue. We therefore assessed the effects of a combination of monalizumab and durvalumab on NK cell activity against K562 cells co-expressing HLA-E and PD-L1 in vitro. description": "The Nankang FT7 All Terrain has a special tread design which increases the tyre rigidity and driving stability.