Key pathogenic hallmarks of PMBCL and pathway perturbation. (A) JAK-STAT and NFκB are key activation pathways in PMBCL leading to transcriptional deregulation and impaired immunogenicity. (B) Mechanisms of immune evasion in PMBCL, including PDL1/2 expression with resultant T-cell anergy, reduced antigenicity through MHC class 2 downregulation (in part, due to CIITA rearrangements and mutations), MHC class 1 defects caused by B2M mutations, and CD58 mutations/microdeletions leading to impaired T- and NK-cell interactions.^8,32,35