Microenvironment, crosstalk, and immune escape mechanisms

Abstract

When discussing the microenvironment in Hodgkin lymphoma (HL), it is important to recognize the different HL subtypes described by the WHO classification. The classical HL (cHL) subtypes are defined in large part by the composition of the reactive infiltrate. The most prevalent subtype is the nodular sclerosis type that consists of a nodular background with thick fibrotic bands, usually with a thickened lymph node capsule. In addition to the lacunar type of Hodgkin/Reed-Sternberg (HRS) cells, there is a microenvironment consisting of T cells, eosinophils, and histiocytes, with a variable admixture of neutrophils, plasma cells, fibroblasts, and mast cells. The second most common subtype is mixed cellularity, which is defined by the presence of typical HRS cells and a diffuse infiltrate of T cells, eosinophils, histiocytes, and plasma cells, sometimes with the formation of granuloma-like clusters or granulomas. Lymphocyte-rich cHL also comprises typical HRS cells in a nodular or diffuse microenvironment and small B and/or T lymphocytes dominating the background, sometimes with admixture of histiocytes. Granulocytes are not a component in this subtype. The rare lymphocyte-depleted subtype harbors a high percentage of HRS cells in a background consisting of fibroblasts and a low number of T cells. Nodular lymphocyte predominance (NLP) HL is considered a separate entity. The morphology may closely resemble that of the nodular variant of the classical lymphocyte-rich subtype, both involving follicular areas with many small B cells. However, the nature of the tumor cells and the T cells is different. In the cHL subtypes, the HRS cells are transformed post germinal center B cells with a loss of B cell phenotype, while in LPHL the lymphocyte-predominant (LP) cells have a germinal center B cell phenotype. The T cells in cHL have features of paracortical T cells, while those in LPHL are similar to germinal center T cells.