In addition, membrane-bound PD-1 also triggered reverse signaling through PD-L1 (Fig. 2a) and treatment with nivolumab inhibited this effect, suggesting that clinical responses in cHL patients to PD-1-blocking antibodies are, at least in part, mediated by interrupting PD-L1 signaling. This evidence concerns the gene PDCD1 and classic Hodgkin lymphoma.