Immune escape mechanisms in B-NHL. Malignant B cells progressively lose surface molecules involved in recognition by CD4 (major histocompatibility complex II), CD8 (major histocompatibility complex I), and NK (CD58) cells, whereas they variably overexpress inhibitory receptors, including PD-L1, LLT1, HVEM, and CD47, which are the ligands for PD-1, CD161, BTLA, and SIRP-α, and produce the inhibitory enzymes IDO and IL4I1. The combination of these mechanisms allows them to avoid killing by cytotoxic cells and phagocytosis by TAM. In addition, they contribute to Treg recruitment and differentiation, as well as to exhaustion of T-effector cells through the release of CCL22, TGF-β, and IL-12 and the expression of ICOSL and CD80/CD86. pAg, phosphoantigen.