High tumour plasma cell infiltration reflects an important microenvironmental component in classic Hodgkin lymphoma linked to presence of B‐symptoms

Abstract

Summary Plasma cells are important prognostic actors in different malignancies. The tumour microenvironmental composition in classic Hodgkin lymphoma (cHL) is a major prognostic key element; however, clinicopathological studies regarding plasma cells in cHL are lacking. The aim of this study was to investigate CD138+ (also termed SDC1+) plasma cell and IgG4 producing (IgG4+) plasma cells infiltration in the microenvironment of cHL. Immunohistochemistry with anti‐CD138 and IgG4 antibodies was performed on diagnostic tumour biopsies from 124 patients with cHL, on tissue micro array (TMA). In 120 cases, CD138+ plasma cell‐infiltration was associated with the presence of B‐symptoms (P = 0·028) and advanced stage, IIB‐IVB (P = 0·009). In multivariate analysis, CD138+ plasma cells correlated with eosinophil infiltration (P = 0·013). The subgroup of IgG4+ plasma cells was analysed in 122 cases and only correlated to CD138+ plasma cells (P = 0·004). Patients with high proportion of tumour infiltrating CD138+ plasma cells (defined as ≥10%), had a more inferior event‐free survival (P = 0·007) and overall survival (P = 0·004) than patients with a low proportion of infiltrating CD138+ plasma cells (<10%), although significance was not maintained in multivariate analysis. In summary, a high proportion of tumour‐associated plasma cells in cHL reflect an important component in the microenvironment of cHL.

Formation of the Immunosuppressive Microenvironment of Classic Hodgkin Lymphoma and Therapeutic Approaches to Counter It

“…TME building in cHL is most likely started and carried out by HRS cells but then is supported by the predominant tumor-educated inflammatory and stromal cells. The cHL TME is composed of numerous CD4-positive T cells and a variable number of eosinophils [24], histiocytes/macrophages [24,25,26], a complex network of B cells [27], mast cells [28], plasma cells [29], fibroblasts [30], mesenchymal stromal cells (MSCs) [31], and endothelial cells [32], as well as a rich extracellular matrix [30]. The TME of EBV-associated cHL is composed of immune cells, including cytotoxic T lymphocytes against EBV-infected HRS cells, and is enriched in histiocytes, dendritic cells, and endothelial cells [14].…”

“…Unfortunately, associations between prognosis and cellular levels, especially of T cells and macrophages, have been studied using different approaches or technologies and often generate different results and conclusions. The abundance of eosinophils and mast cells has been associated with poor prognosis, but the results have not been confirmed [24,29,90].…”

The Immunosuppressive Microenvironment of Classic Hodgkin Lymphoma and Therapeutic Approaches to Counter It

“…Unfortunately, associations between prognosis and cellular levels, especially of T cells and macrophages, have been studied using different approaches or technologies and often generate different results and conclusions. The abundance of eosinophils and mast cells has been associated with poor prognosis, but the results have not been confirmed [24,29,60].…”

“…TME building in cHL is most likely started and carried out by HRS cells but then is supported by the predominant tumor-educated inflammatory and stromal cells. The cHL TME is composed of numerous CD4-positive T cells and a variable number of eosinophils [24], histiocytes/macrophages [24][25][26], a complex network of B cells [27], mast cells [28], plasma cells [29], fibroblasts [30], mesenchymal stromal cells (MSCs) [31], endothelial cells [32], and a rich extracellular matrix [30].…”

Plasma cells in classical Hodgkin lymphoma: a new player in the microenvironment?

“…A new paper (Gholiha et al , ) in this issue of the British Journal of Haematology, explored the role of plasma cells in the survival and clinical parameters of cHL. This study investigated a more recent Swedish patient cohort of 120 patients, collected within 3 years and with uniform modern treatment.…”