Publications by authors named "Martin-Leo Hansmann"

Article Synopsis
  • - The lymph node is structured into dynamic compartments like T and B zones, which enhance both innate and adaptive immune responses and have led to new insights across various biological and medical fields.
  • - The review emphasizes advanced 3D and 4D imaging techniques to study human lymph nodes, highlighting the insights gained from these methods compared to traditional 2D tissue analysis, particularly in understanding immune interactions and lymphoma behavior.
  • - Findings show that T cells move faster than B cells and reticulum cells within reactive lymphoid tissue, with variations in cell contact times potentially aiding in lymphoma classification; 4D technology can also play a key role in testing new cancer therapies.
View Article and Find Full Text PDF
Article Synopsis
  • Normal and malignant B cells have unique immunoglobulin (Ig) genes that can act as markers due to their high diversity.
  • A laser-based microdissection method is used to isolate single B cells from frozen tissue sections and amplify specific rearranged Ig genes through semi-nested PCR.
  • Analyzing these genes allows researchers to determine the clonal relationships of B cells, their gene usage, and their differentiation stage based on mutation patterns.
View Article and Find Full Text PDF
Article Synopsis
  • - Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive B-cell lymphoma, and its subtypes have varying outcomes, prompting efforts to better predict patient prognosis based on cell origin.
  • - This study focused on analyzing the migration abilities of two genetic subtypes of DLBCL, MCD and EZB, using specific tests to measure their movement through microchannels and narrow spaces.
  • - Results showed that EZB-type cells migrated faster and more effectively through constrictions than MCD-type cells, which had higher levels of a protein affecting nuclear stiffness, suggesting that genetic differences may impact both therapy outcomes and tumor cell motility.
View Article and Find Full Text PDF

Although checkpoint molecules like CTLA-4 and PD1 have been described several years ago, checkpoint inhibitors such as nivolumab (an anti-PD-1 antibody) have only recently been used to treat classic Hodgkin lymphoma (cHL). Several studies have shown convincing therapeutic effects of nivolumab in cHL. However, the mechanism of action of nivolumab in cHL is not fully understood.

View Article and Find Full Text PDF
Article Synopsis
  • Type 1 diabetes happens when the body's immune system mistakenly attacks and destroys insulin-producing cells in the pancreas.
  • Treatment mainly involves giving insulin from outside the body, and there are not many other therapies that can target the immune system directly.
  • In a study with mice, researchers found specific proteins and genes related to inflammation in the pancreas that could help with new treatments, especially focusing on how certain chemicals called chemokines make immune cells move around and cause problems.
View Article and Find Full Text PDF

Background: Lymph-node diagnostics is performed using thin sections, with help of immunohistochemistry by light microscopy and supplemented by molecular pathology.

Objectives: Which are the scientific and diagnostic perspectives of 3D and 4D lymph node investigations, using laser, scanning, and computer technologies? What is the impact of machine learning in complex data analysis.

Results: It was shown in different investigations that the analysis in space and time (3D/4D) of lymph node tissue is able to provide a lot of new information concerning biology and diagnostics and enable excellent evaluations applying machine learning.

View Article and Find Full Text PDF

Standardized treatment options are lacking for patients with unresectable or multifocal follicular dendritic cell sarcoma (FDCS) and disease-related mortality is as high as 20%. Applying whole-genome sequencing (WGS) in one case and whole-exome sequencing (WES) in additional twelve cases, this study adds information on the molecular landscape of FDCS, expanding knowledge on pathobiological mechanisms and identifying novel markers of potential theragnostic significance. Massive parallel sequencing showed high frequency of mutations on oncosuppressor genes, particularly in RB1, CARS and BRCA2 and unveiled alterations on homologous recombination DNA damage repair-related genes in 70% (9/13) of cases.

View Article and Find Full Text PDF

Disease-causing mutations in genes encoding transcription factors (TFs) can affect TF interactions with their cognate DNA-binding motifs. Whether and how TF mutations impact upon the binding to TF composite elements (CE) and the interaction with other TFs is unclear. Here, we report a distinct mechanism of TF alteration in human lymphomas with perturbed B cell identity, in particular classic Hodgkin lymphoma.

View Article and Find Full Text PDF
Article Synopsis
  • Researchers studied two types of follicular lymphoma (FL): localized (lFL) and systemic (sFL) to understand how they develop.
  • They looked at 147 cases of lFL and 122 cases of sFL, using special methods to check for genetic changes.
  • They found that while both types have some similarities, there are important differences, like certain genetic changes that might affect how long people live without the disease worsening.
View Article and Find Full Text PDF

Introduction: Normal CD30 B cells represent a distinct B-cell differentiation stage with features of strong activation. We lack an in depth understanding of these cells, because they are not present in peripheral blood and are typically very rare in reactive lymphoid organs. CD30 B cells have been discussed as a potential precursor population for the malignant CD30 Hodgkin and Reed-Sternberg cells in classical Hodgkin lymphoma.

View Article and Find Full Text PDF

Germinal centers (GCs) are some of the most important structures in the human immune system. As such, their cell types and functions have been thoroughly investigated. B cells, T cells, follicular dendritic cells (FDCs), and macrophages have widely been found to typically be aggregated in GCs.

View Article and Find Full Text PDF

Nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (AITL), is characterized by constitutional symptoms, advanced-stage disease, and generalized lymphadenopathy. A genetic hallmark of this lymphoma is the frequent occurrence of the mutation G17V in neoplastic cells, which is observed in around 60% of patients. Because is involved in both T-cell receptor downstream signalling and cell migration, we hypothesized that the characteristic presentation of AITL could be the result of enhanced tumor cell migration.

View Article and Find Full Text PDF
Article Synopsis
  • - Kikuchi-Fujimoto disease (KFD) is a relatively harmless condition that mainly causes swollen lymph nodes in young women and can be mistaken for more serious diseases due to similar T-cell features.
  • - A recent study analyzed 88 KFD cases to see if clonal T-cell receptor (TCR) amplifications could be detected, finding clonal peaks in 18% of cases without significant differences in other clinical parameters.
  • - The findings suggest that while clonal TCR gamma results can occur in KFD, care must be taken not to misinterpret these as signs of a serious illness, like T-cell neoplasia.
View Article and Find Full Text PDF

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a Hodgkin lymphoma expressing functional B-cell receptors (BCR). Recently, we described a dual stimulation model of IgD+ lymphocyte-predominant cells by Moraxella catarrhalis antigen RpoC and its superantigen MID/hag, associated with extralong CDR3 and HLA-DRB1*04 or HLADRB1* 07 haplotype. The aim of the present study was to extend the antigen screening to further bacteria and viruses.

View Article and Find Full Text PDF

MicroRNAs (miRNAs) are small non coding RNAs responsible for posttranscriptional regulation of gene expression. Even though almost 2000 precursors have been described so far, additional miRNAs are still being discovered in normal as well as malignant cells. Alike protein coding genes, miRNAs may acquire oncogenic properties in consequence of altered expression or presence of gain or loss of function mutations.

View Article and Find Full Text PDF

The simulation of immune response is a challenging task because quantitative data are scarce. Quantitative theoretical models either focus on specific cell-cell interactions or have to make assumptions about parameters. The broad variation of, e.

View Article and Find Full Text PDF

Treatment of vascular stenosis with angioplasty results in acute vascular damage, which may lead to restenosis. Owing to the highly complex cellularity of blood vessels, the healing response following this damage is incompletely understood. To gain further insight into this process, scRNA-seq of mouse carotid tissue after wire injury was performed.

View Article and Find Full Text PDF

Histological sections of the lymphatic system are usually the basis of static (2D) morphological investigations. Here, we performed a dynamic (4D) analysis of human reactive lymphoid tissue using confocal fluorescent laser microscopy in combination with machine learning. Based on tracks for T-cells (CD3), B-cells (CD20), follicular T-helper cells (PD1) and optical flow of follicular dendritic cells (CD35), we put forward the first quantitative analysis of movement-related and morphological parameters within human lymphoid tissue.

View Article and Find Full Text PDF

Burkitt lymphoma (BL) represents the most aggressive B-cell-lymphoma. Beside the hallmark of -translocation, surface B-cell receptor (BCR) is expressed, and mutations in the BCR pathway are frequent. Coincidental infections in endemic BL, and specific extra-nodal sites suggest antigenic triggers.

View Article and Find Full Text PDF

Recently, we have developed novel highly promising gene expression (GE) classifiers discriminating localized nodal (LFL) from systemic follicular lymphoma (SFL) with prognostic impact. However, few data are available in LFL especially concerning hotspot genetic alterations that are associated with the pathogenesis and prognosis of SFL. A total of 144 LFL and 527 SFL, enrolled in prospective clinical trials of the German Low Grade Lymphoma Study Group, were analyzed by fluorescence in situ hybridization to detect deletions in chromosomes 1p, 6q, and 17p as well as translocations to determine their impact on clinical outcome of LFL patients.

View Article and Find Full Text PDF

Lymph node-infiltrating T cells have been of particular interest in classical Hodgkin lymphoma (cHL). High rates of complete therapeutic responses to antibody-mediated immune checkpoint blockade, even in relapsed/refractory patients, suggest the existence of a T cell-dominated, antigen-experienced, functionally inhibited and lymphoma-directed immune microenvironment. We asked whether clonally expanded T cells (1) were detectable in cHL lymph nodes, (2) showed characteristic immune phenotypes, and (3) were inhibited by immune checkpoint molecule expression.

View Article and Find Full Text PDF

The human body comprises around 600 lymph nodes as constituents of a decentralized and dispersed immune system. The main task of lymph nodes is cleaning the lymph fluid and defending the organism against outer and inner threats by bacteria, viruses and tumour cells. The histologic picture of lymph nodes reflects the different strategies of the innate and adaptive immune system, which allocates antigen presenting cells, macrophages, B‑ and T‑cell systems and reticulum cells.

View Article and Find Full Text PDF

Different studies have characterized the microenvironment and its prognostic impact in classic Hodgkin lymphoma whereas such analyses are pending for nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). We thus investigated characteristics of tumour cells and microenvironment in NLPHL and evaluated possible correlations with the clinical presentation. Lymph node samples from 152 NLPHL patients who had first-line treatment within the randomized German Hodgkin Study Group HD16-HD18 trials were available and analysed with regard to IgD status and nuclear size of the tumour cells as well as presence of PD1-positive follicular T helper cells and CD163-positive macrophages in the microenvironment.

View Article and Find Full Text PDF

Classic Hodgkin lymphoma (cHL) is usually characterized by a low tumour cell content, derived from crippled germinal centre B cells. Rare cases have been described in which the tumour cells show clonal T-cell receptor rearrangements. From a clinicopathological perspective, it is unclear if these cases should be classified as cHL or anaplastic large T-cell lymphoma (ALCL).

View Article and Find Full Text PDF