Microenvironment, crosstalk, and immune escape mechanisms

Hodgkin lymphoma is a unique malignancy in which reactive immune cells vastly outnumber the tumor cells. The microenvironment is essential in many different aspects of Hodgkin lymphoma biology and has ramifications for diagnosis, clinical presentation, and therapeutic options. In this chapter we review current knowledge on the Hodgkin lymphoma microenvironment. Its composition is highly variable and provides the basis for diagnostic subtyping. T cells are virtually always present and usually cluster together with the tumor cells in so-called rosettes. We describe mechanisms by which the tumor cells actively shape their cellular environment and how this ensures recruitment of tumor cell promoting growth factors. The tumor cells also need to employ a variety of immune escape mechanisms with a central role for antigen presentation through the human leukocyte antigen and associated immune checkpoints. Given the different pathogenetic functions of different cell types in the microenvironment, we end with reviewing data on the prognostic impact of the abundance of specific cell types.