Landscape of 4D Cell Interaction in Hodgkin and Non-Hodgkin Lymphomas

Simple Summary: Little is known about the motility and interaction of primary human lymphoma cells in lymph nodes. The aim of this study therefore was to analyze for the first time if there are differences in motility and interaction with bystander cells between different lymphoma types and normal lymph nodes. We observed systematic differences between B cells and PD1-positive T cells. Furthermore, most cases of Hodgkin lymphomas had fast moving PD1-positive T cells, whereas there was little movement in other lymphoma types. Some lymphomas, particularly Hodgkin lymphomas, presented enhanced cell contacts between neoplastic and reactive cells, suggesting a dependency of lymphoma growth on cellular interaction. Profound knowledge exists about the clinical, morphologic, genomic, and transcriptomic characteristics of most lymphoma entities. However, information is currently lacking on the dynamic behavior of malignant lymphomas. This pilot study aimed to gain insight into the motility of malignant lymphomas and bystander cells in 20 human lymph nodes. Generally, B cells were faster under reactive conditions compared with B cells in malignant lymphomas. In contrast, PD1-positive T cells did not show systematic differences in velocity between reactive and neoplastic conditions in general. However, lymphomas could be divided into two groups: one with fast PD1-positive T cells (e.g., Hodgkin lymphoma and mantle cell lymphoma; means 8.4 and 7.8 mu m/min) and another with slower PD1-positive T cells (e.g., mediastinal grey zone lymphoma; mean 3.5 mu m/min). Although the number of contacts between lymphoma cells and PD1-positive T cells was similar in different lymphoma types, important differences were observed in the duration of these contacts. Among the lymphomas with fast PD1-positive T cells, contacts were particularly short in mantle cell lymphoma (mean 54 s), whereas nodular lymphocyte-predominant Hodgkin lymphoma presented prolonged contact times (mean 6.1 min). Short contact times in mantle cell lymphoma were associated with the largest spatial displacement of PD1-positive cells (mean 12.3 mu m). Although PD1-positive T cells in nodular lymphocyte-predominant Hodgkin lymphoma were fast, they remained in close contact with the lymphoma cells, in line with a dynamic immunological synapse. This pilot study shows for the first time systematic differences in the dynamic behavior of lymphoma and bystander cells between different lymphoma types.