Figure 6. TIGIT engagement inhibits pZAP70/Syk and pERK1/2 and results in inhibition of NK cell cytotoxicity.

A) Purified NK cells were co-cultured with MDSCs or monocytes at a 2:1 ratio in the presence of IL-15 (10 ng/ml), IgG control (10 μg/ml) and in the presence or absence of blocking antibodies against TIGIT (10 μg/ml), or catalase (200 IU/mL) for 5 days. Cells were stimulated for 10 and 30 min with anti-CD16, and stained for pZAP/Syk or pERK1/2 respectively. Representative A) or cumulative B) data are shown from 3 independent experiments and 6 donors as mean ± SEM. Statistical analysis were done using the Two-Way ANOVA. C) NK cells from monocyte and MDSC co-cultures in the presence or absence of anti-TIGIT or catalase were washed and incubated with ⁵¹Cr-labeled K562 for 4 hours to assess NK cell cytotoxicity. Representative data from 3 independent experiments is shown as mean ± SEM.