Godfrey J, et al. - Researchers used FISH to investigate diffuse large B-cell lymphomas (DLBCLs) harboring programmed death-ligand 1 (PD-L1) gene changes, to characterize the immunogenomic landscape of these lymphomas. Among non-germinal center DLBCLs, PD-L1 changes were highly enriched and showed strong PD-L1 protein expression. Heavy infiltration by clonally-restricted T cells was seen in these lymphomas. In addition, these lymphomas frequently down-regulated human leukocyte antigen expression. After front-line chemo-immunotherapy, inferior progression-free survival was seen in DLBCL patients with PD-L1 alterations, however, a link between PD-L1 alterations and response to anti-PD-1 therapy was noted in the relapsed/refractory setting. Overall, a unique biological subset of DLBCL was identified by PD-L1 alterations. In this subset, an endogenous anti-lymphoma immune response has been activated, and which was related to responsiveness to PD-1 blockade therapy.