Mechanisms associated with inflamed lymphoma environments. (A) Acquisition of oncogenic alterations that drive increased expression of NF-κB pathway members or those resulting in the deletion or inactivation of NF-κB regulatory genes culminate in enhanced lymphoma cell-intrinsic NF-κB signaling and transcription of pro-survival genes, as well as those encoding pro-inflammatory cytokines and chemokines. The latter may lead to enhanced recruitment and sustained activation of immune cells in the lymphoma environment. (B) A subset of inflamed lymphomas, including cHL and PMBL, exhibit microsatellite instability and/or apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) mutational signatures, which have been associated with increased generation of neo-antigens that can be targeted by host T cells. Alternatively, malignant cells in some cHL and DLBCL are associated with EBV infection, and EBV-derived viral epitopes can drive T-cell responses, particularly in the context of cHL.