Of note, the modest efficacy observed for CLL patients, which was limited to patients with the aggressive Richter transformation who experienced increased PD-1 expression during treatment (Ding et al., 2017; Kline et al., 2020; Ioannou et al., 2021), together with the large variability of both PD-1 and PD-L1 expression in CLL patients, underlie the low effectiveness of neutralizing antibody-based therapies (Brusa et al., 2013; Ding et al., 2017) and highlight the need of alternative therapeutic approaches to target this signaling axis in CLL. Here, CD274 is linked to B-cell chronic lymphocytic leukemia.