Abstract

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is characterized by a low percentage of neoplastic lymphocyte predominant (LP) cells in a background of lymphocytes. The goal of this study is to characterize the microenvironment in NLPHL. Ten NLPHL cases and seven reactive lymph nodes (RLN) were analyzed by flow cytometry for the main immune cells and multiple specific subpopulations. To discriminate between cells in or outside the tumor cell area, we used CD26. We observed significantly lower levels of CD20+ B-cells and CD56+ NK cells and higher levels of CD4+ T-cells in NLPHL in comparison to RLN. In the subpopulations, we observed increased numbers of PD-1+CD4+ T follicular helper cells (TFH), CD69+CD4+ and CD69+CD8+ T-cells and CCR7-CD45RA-CD4+ effector memory T-cells, while FoxP3+CD4+ T regulatory cells (Tregs) and CCR7-CD45RA+ terminally differentiated CD4+ T-cells were decreased in NLPHL compared to RLN. CD69+ cells were increased in the tumor cell area in CD4+ and CD8+ T-cells, while FoxP3+CD25+CD4+ Tregs and CD25+CD8+ T-cells were significantly increased outside the tumor area. Thus, we show a markedly altered microenvironment in NLPHL, with lower numbers of NK cells and Tregs. PD-1+CD4+ and CD69+ T-cells were located inside, and Tregs and CD25+CD8+ cells outside the tumor cell area.

Highlights

  • The lower number of NK cells in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) compared to reactive lymph nodes (RLN) has not been reported previously

  • The subpopulation that showed the most prominent increase in NLPHL compared to RLN is PD-1+CD4+ T-cell subset, and these cells have been reported to surround the lymphocyte predominant (LP) cells [4]

  • Since the IL21 receptor is upregulated in LP cells [12], and IL-21 is produced by T follicular helper cells (TFH) cells, these cells might be beneficial for survival of LP cells

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Summary

Introduction

Hodgkin Lymphoma (HL) is a unique type of B-cell lymphoma characterized by presence of a minority of neoplastic cells (less than 1%) in a background of infiltrating reactive cells [1]. Based on differences in histopathology and neoplastic cells, HL is classified in two subgroups: classical (c)HL and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). CHL accounts for 95% of all HL cases, whereas NLPHL accounts for only 5% of all cases [1]. Both the neoplastic cells of NLPHL, i.e., the lymphocyte predominant (LP) cells, and the composition of the cells present in the microenvironment of NLPHL are different from cHL. In cHL increased numbers of Tregulatory (Treg) cells [7,8], and an increased number of T helper (Th)2 [3] and Th1 [9] cells has been reported

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