To explain the increased anti-myeloma immunity after WBI and checkpoint blockade, we have proposed the following model: (a) PD-1+ tumor-reactive CD8 T cells are rendered dysfunctional upon encounter with PD-L1 and other checkpoint ligands on the myeloma cells (5T33 expresses high levels of PD-L1) [39] or other cells in the microenvironment, (b) that the PD-1+ cells are able to recover function after WBI due to the transient lymphopenic state through mechanisms yet to be identified, and (c) ongoing checkpoint blockade is required to maintain function of the re-activated T cells. This evidence concerns the gene CD274 and plasma cell myeloma.