Fig. 3: Immune evasion mechanisms in cHL.

Shown are main mechanisms how HRS cells escape from an attack by cytotoxic T cells and NK cells. Several factors promote the production and reduce the degradation of extracellular adenosin (ADO), which inhibits the function of CD8⁺ T cells (see main text). Indoleamine 2,3-dioxygenase (IDO) is intracellularly expressed by macrophages and dendritic cells (not shown) in the HL microenvironment and reduces the extracellular levels of tryptophan, which impairs the function of cytotoxic T cells and NK cells. The immunosuppressive function of CD137 is thought to be mediated in an indirect fashion: CD137 on HRS cells and CD137 transmitted to other immune cells through trogocytosis promote the internalization of CD137L, thereby reducing the level of this costimulatory factor for T cell activity. The downregulation of NKG2D-L on HRS cells is mediated by exoenzymes that cleave it from the surface of HRS cells. Whereas MHC class I is downregulated by most cases of cHL, loss of MHC class II expression is seen only in a subset of cases.