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

被引:11
作者
Hartmann, Sylvia [1 ]
Scharf, Sonja [2 ,3 ]
Steiner, Yvonne [1 ]
Loth, Andreas G. [4 ]
Donnadieu, Emmanuel [5 ]
Flinner, Nadine [1 ,2 ]
Poeschel, Viola [6 ]
Angel, Stephanie [6 ]
Bewarder, Moritz [6 ]
Bein, Julia [1 ]
Brunnberg, Uta [7 ]
Bozzato, Alessandro [8 ]
Schick, Bernhard [8 ]
Stilgenbauer, Stephan [6 ,9 ]
Bohle, Rainer M. [10 ]
Thurner, Lorenz [6 ,11 ]
Hansmann, Martin-Leo [2 ,12 ]
机构
[1] Goethe Univ Frankfurt Main, Dr Senckenberg Inst Pathol, Theodor Stern Kai 7, D-60590 Frankfurt, Germany
[2] Frankfurt Inst Adv Studies, D-60438 Frankfurt, Germany
[3] Goethe Univ Frankfurt Main, Mol Bioinformat, Inst Comp Sci, Robert Mayer Str 11-15, D-60325 Frankfurt, Germany
[4] Univ Hosp Frankfurt, Dept Otolaryngol Head & Neck Surg, D-60590 Frankfurt, Germany
[5] Univ Paris, Inst Cochin, INSERM U1016/, CNRS UMR 8104, F-75014 Paris, France
[6] Saarland Univ, Internal Med 1, Sch Med, D-66421 Homburg, Germany
[7] Goethe Univ Hosp, Dept Internal Med 2, D-60590 Frankfurt, Germany
[8] Saarland Univ, Dept Otorhinolaryngol Head & Neck Surg, Med Ctr, D-66421 Homburg, Germany
[9] Univ Hosp Ulm, Comprehens Canc Ctr Ulm CCCU, D-89070 Ulm, Germany
[10] Saarland Univ, Inst Pathol, Med Sch, D-66421 Homburg, Germany
[11] Saarland Univ, Jose Carreras Ctr Immuno & Gene Therapy, Med Sch, D-66421 Homburg, Germany
[12] Goethe Univ Frankfurt Main, Inst Gen Pharmacol & Toxicol, Theodor Stern Kai 7, D-60590 Frankfurt, Germany
关键词
migration; cell motility; cell contacts; Hodgkin lymphoma; non-Hodgkin lymphoma; FOLLICULAR LYMPHOMA; CLASSIFICATION; POPULATION; SIGNATURES; MUTATIONS; MIGRATION; MOTILITY;
D O I
10.3390/cancers13205208
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页数:14
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