One possible explanation is that, in addition to the PD-L1/PD-1 interaction, PD-L1 and PD-1 also engage CD80 and PD-L2, respectively, which could lead to distinct αPD-L1 and αPD-1 effects, especially if these additional protein partners of PD-L1/PD-1 are differentially affected by obesity as is known for PD-1 and PD-L1 41,42. Here, CD274 is linked to obesity due to melanocortin 4 receptor deficiency.