Satisfactory results in terms of response rate have been observed when PD-1-blocking mAbs were used, alone or in association with ibrutinib, in CLL patients, especially those with high levels of PD-L1 and PD-1 in the tumor microenvironment [20,253], undergoing Richter’s syndrome, a CLL transformation to aggressive lymphoma, mainly occurring as diffuse large B cell lymphoma [254]. Here, CD274 is linked to B-cell chronic lymphocytic leukemia.