Schematic diagram summarizing immune escape mechanisms of PMBL. PMBL tumors can harbor multiple genetic alterations, including mutations, indels, and copy number alterations, which enable them to evade tumor immunosurveillance. These general approaches to immune evasion firstly include alterations in antigen presentation such as rearrangements, indels, and mutations of the CIITA gene, which encodes the master transactivator of the major histocompatibility complex (MHC) class II molecules; mutations in the gene encoding the invariant chain CD58, also known as the lymphocyte adhesion molecule LFA-3, that in the wild-type state, strengthens the adhesion between the antigen-presenting cell (in this case, the PMBL cell) and reactive T cells; and mutations in the gene encoding β-2 microglobulin (B2M), which in the wild-type state, normally stabilizes the MHC class I molecules to activate CD8⁺ T cells. Secondly, T-cell activation is affected by amplification of the genes encoding programmed death-ligand 1 (PD-L1) and PD-L2, which bind the inhibitory checkpoint molecule programmed cell death protein 1 (PD-1) on antigen-specific T cells. Thirdly, natural killer (NK) cells and macrophages are affected by mutations in the interferon regulatory response cytokines and downstream genes which, in the wild-type state, upregulate antigen presentation via MHC.