[Microenvironment in classical Hodgkin lymphoma]

Classical Hodgkin lymphoma (cHL) is histologically characterized by a quantitatively dominating immune cell infiltrate. Its composition differs depending on the histological subtype and EBV (Epstein-Barr-Virus) status. Current pathogenic concepts postulate that the malignant cells, the so-called Hodgkin and Reed-Sternberg (HRS) cells, act as master recruiters, thereby actively shaping the microenvironment to support their proliferation and outgrowth. This view on the pathogenesis of cHL is further solidified by genetic studies, which have identified important mechanisms by which the HRS cells are enabled to escape immune surveillance. Besides an insufficient antigen presentation mediated by mutations and structural chromosomal changes in key components or regulators of major histocompatibility class I and II molecules, copy number gains of the 9p24.1 genomic locus encompassing JAK2 and the ligands of the programmed cell death protein 1 (PD-1), PD-L1 and PD-L2, play an important role in the pathogenesis of this disease as the engagement of those ligands with their cognate receptor leads to suppression of the immune response. Of importance, the reversibility of this inhibitory receptor-ligand interaction is key to the clinical success that checkpoint inhibitors had and continue to have in cHL patients, especially in the relapse setting. In addition, comprehensive assessment of microenvironment composition, integration with results from genetic studies, and correlation with clinical outcomes have led to the development of prognostic models, which may assist in an improved risk stratification, informed selection of treatment regimens, and therefore better outcomes.