Novel Insights From Lymphoid Structures: Lessons From Colorectal Cancer Research

Sponsored Content by TissueGnosticsReviewed by Maria OsipovaJul 31 2025

In this interview, we said pinch Associate Professor Diana Mechtcheriakova astir really lymphoid structures and germinal centers are unlocking caller prognostic insights into colorectal cancer, and pinch Anastasiia Marchuk of TissueGnostics astir nan imaging technologies powering this research.

Can you please present yourself and your domiciled astatine nan Medical University of Vienna?

Diana Mechtcheriakova: I americium Diana Mechtcheriakova, affiliated pinch nan Institute of Pathophysiology and Allergy Research astatine nan Medical University of Vienna, wherever I service arsenic caput of nan investigation group Molecular Systems Biology and Pathophysiology.

My caller presentation, titled "Unlocking nan Lymphoid Structures pinch Germinal Centers: Architectural Complexity, Functionality, and Clinical Relevance," reflects nan halfway themes of our research.

Our group operates wrong a conceptual model that transitions from systems biology to systems medicine, aligning pinch nan broader imagination of personalized medicine. This attack is based connected nan Aristotelian rule that “the full is greater than nan sum of its parts” and emphasizes a holistic methodology for deciphering biologic complexity done a hierarchical travel from information to accusation to knowledge.

Our superior investigation areas see nan improvement of systems biology approaches applied to various projects, pinch a attraction connected B-cell biology, immune oncology, lymphoid structures, AID/APOBEC-associated biologic events, and nan cellular sphingolipid/lysophosphatidate strategy successful immunity and cancer.

In addition, I lead nan Tissue Image Cytometry Unit astatine Austrian Bioimaging and service arsenic caput of nan Basic and Translational Research Module astatine nan Austrian Platform for Personalized Medicine.

Could you show america much astir your caller investigation connected lymphoid structures and their objective relevance successful cancer?

Diana Mechtcheriakova: My caller activity focuses connected nan biology of lymphoid structures, which are highly organized formations characterized by dense cellular interactions and functional practice among various immune compartment types. These see B-cell subsets, follicular helper T cells, and follicular dendritic cells.

When afloat developed, these structures incorporate germinal centers, which are functional niches wherever B cells proliferate, differentiate, acquisition affinity maturation, and move antibody classes. A cardinal marker of progressive germinal centers is activation-induced cytidine deaminase (AID), which tin beryllium visualized done insubstantial staining, specified arsenic successful tonsil samples.

The germinal halfway guidance results successful nan accumulation of plasma cells and representation B cells. These lymphoid structures are typically located successful secondary lymphoid organs; however, they tin besides beryllium assembled successful ectopic locations wrong chronically inflamed tissues, including tumors. In specified cases, they are referred to arsenic ectopic lymphoid structures (ELS) aliases tertiary lymphoid structures (TLS).

A peculiarly important facet of this investigation is nan objective relevance of B cells and ELS successful cancer. It has been demonstrated—an penetration I see 1 of nan awesome breakthroughs of caller years—that nan section beingness of B cells and ectopic lymphoid structures correlates pinch favorable diligent prognosis successful much than 10 crab types. Notable examples see non-small compartment lung cancer, bosom cancer, and colorectal crab pinch liver metastases.

Can you picture your investigation findings connected ectopic lymphoid structures successful colorectal crab pinch liver metastases?

Diana Mechtcheriakova: In nan discourse of colorectal crab pinch liver metastases, our investigation group was among nan first to show nan accumulation of B cells assembled successful ectopic lymphoid structures (ELS) pinch progressive germinal centers successful nan liver. These ELS were observed forming a ring-like shape astir nan metastases.

To analyse this further, we conducted a precise quantification of B cells and ELS astatine nan tumor-liver interface, utilizing defined zones extending some toward nan tumor and into nan adjacent liver tissue. This study was performed done quantitative insubstantial image cytometry, utilizing TissueFAXS-based computerized microscopy. Our findings revealed that a higher density of B cells and ELS astatine nan tumor-liver separator correlated pinch improved objective outcomes, peculiarly successful position of diligent survival.

This prognostic worth exceeded that of accepted clinicopathological parameters. Based connected these observations, we projected nan presumption that nan anti-tumor immune consequence astatine nan metastatic tract successful nan liver whitethorn beryllium pre-instructed either astatine nan superior colorectal crab tract aliases perchance wrong nan non-tumorous colon mucosa, wherever isolated lymphoid structures (ILS) are usually present.

Image Credit: Anusorn Nakdee/Shutterstock.com

What was nan superior nonsubjective of your study connected lymphoid structures successful metastatic colorectal cancer?

Diana Mechtcheriakova: The main nonsubjective of our study was to find whether circumstantial characteristics of lymphoid structures crossed 3 chopped insubstantial entities power nan pathobiology of metastatic colorectal crab (CRC). To analyse this, we developed a multi-modular attack called DIICO, which stands for Digital Immune Imaging to Clinical Outcome.

The first module of nan DIICO strategy progressive immunostaining insubstantial samples utilizing a defined group of immune markers. These included CD20 arsenic a wide B-cell marker, AID to place functionally progressive germinal centers, Ki67 for proliferating cells, CD27 for representation B cells and plasma cells, CD138 for plasma cells, and CD3 arsenic a wide T-cell marker.

We applied these markers to some colon crab specimens and tonsil tissues to qualify nan immune compartment creation and measure nan functional activity of lymphoid structures.

How did you instrumentality nan DIICO strategy, and what did your insubstantial study reveal?

Diana Mechtcheriakova: The 2nd module of nan DIICO strategy focused connected assessing nan immunological imprint utilizing quantitative insubstantial image cytometry. Stained specimens were digitized done nan automated microscope-based TissueFAXS platform, and quantitative study was performed utilizing nan HistoQuest and TissueQuest package packages.

Lymphoid structures were defined arsenic chopped objects, and nan study was carried retired astatine nan single-cell level pinch marker-positive compartment discovery based connected circumstantial look profiles.

We person had nan TissueFAXS level astatine our institute since 2008, and successful 2022, we were recognized arsenic a Center of Excellence for Quantitative Digital Microscopy. For this task alone, we analyzed much than 700 colon crab insubstantial slides and complete 120 tonsil samples.

This study transformed tissue-encoded accusation into numerical variables, categorized by anatomical region and staining characteristics for each patient. These variables were past aligned pinch clinicopathological parameters to make insights into illness mechanisms and diligent outcomes.

What did your study uncover astir nan objective value of lymphoid building characteristics successful metastatic colorectal cancer?

Diana Mechtcheriakova: In our study, we identified 24 variables related to lymphoid building characteristics. These included parameters specified arsenic anatomical site, number and size of lymphoid structures, cellular density, and nan percent of marker-positive cells for each defined immune marker.

A cardinal mobility we addressed was nan objective relevance of these variables successful characterizing nan immune phenotype of lymphoid structures. Notably, successful non-tumorous (NT) tissue, we recovered that variables reflecting nan percent of CD20-positive B cells and Ki67-positive proliferating cells—individually and successful combination—demonstrated beardown prognostic value.

This was supported by statistically important diligent stratification into low- and high-risk groups utilizing Kaplan-Meier endurance estimates. One of nan astir important findings was that B-cell-enriched and highly proliferative isolated lymphoid structures (ILS) located successful nan non-tumorous colonic mucosa had a pronounced effect connected diligent endurance outcomes.

This find indicates that nan immunological imprint of lymphoid structures successful normal colon insubstantial encodes valuable prognostic accusation for patients pinch colorectal crab liver metastases.

What are nan adjacent steps successful your investigation connected lymphoid structures?

Diana Mechtcheriakova: Building upon our systems biology-based, multi-modular study strategy, we are now expanding our attack beyond quantitative insubstantial image cytometry—powered by nan TissueFAXS platform—and transcriptomic information study done nan GENEVESTIGATOR tool.

We person precocious integrated 2 further modules into our framework. The first is spatial transcriptomics utilizing 10x Genomics Visium Spatial Gene Expression, which enables mRNA profiling straight wrong FFPE insubstantial sections, preserving spatial context.

The 2nd is nan exertion of artificial intelligence successful biomedical research, introduced done our caller ongoing project, LymphoidStructureMiner, successful collaboration pinch AI specialists from Danube Private University successful Austria.

Through nan mixed powerfulness of these technologies, we purpose to create precocious analytical models to further unravel germinal halfway biology. Our eventual extremity is nan recognition of caller biomarkers and therapeutic targets to heighten precision successful crab test and treatment.

Could you present TissueGnostics and explicate really your technologies, particularly insubstantial cytometry, support precocious research?

Anastasiia Marchuk: My sanction is Anastasiia Marchuk, and I correspond TissueGnostics, a institution headquartered successful Vienna, Austria. We person been progressive successful nan section for complete 20 years, specializing successful full descent imaging and image analysis. Our halfway attraction is connected a method we mention to arsenic insubstantial cytometry, which involves detecting and phenotyping cells wrong their autochthonal insubstantial microenvironment.

The instauration of insubstantial cytometry is single-cell analysis, wherever individual cells—typically identified by atomic staining—are detected and quantified. To specify compartment phenotypes, circumstantial discovery profiles are applied, allowing for quantification and characterization done spatial phenotyping. This process not only identifies compartment types but besides analyzes their spatial distribution wrong nan tissue.

Tissue cytometry supports multicellular building detection, enabling nan study of anatomical features specified arsenic colon crypts, humor vessels, aliases glomeruli. It besides facilitates nan quantification of cellular pathogens and nan elaborate characterization of intracellular content.

We connection civilization study solutions successful nan shape of pre-configured, application-specific pipelines designed to reside targeted investigation questions. For full descent imaging, we supply TissueFAXS modular systems, which are afloat automated platforms tin of processing immunofluorescence (IF) aliases immunohistochemistry (IHC) stained tissues aliases cells connected solid slides, good plates, aliases insubstantial microarrays.

These systems are disposable successful some upright and inverted configurations, pinch support for brightfield, fluorescence, aliases mixed modalities, depending connected investigation needs. Once a descent is placed and acquisition settings are selected, nan automated strategy generates a afloat digitized image, allowing researchers to attraction connected different tasks while nan imaging is completed.

What precocious image study capabilities does TissueGnostics offer, and what innovations are you moving connected for nan future?

Anastasiia Marchuk: TissueGnostics provides elastic and powerful imaging solutions designed to support a wide scope of investigation needs. Users tin specify their ain study pipelines and customize imaging settings, which tin beryllium saved and reused to guarantee consistency crossed experiments.

As a modular and afloat automated system, we besides connection configurations for confocal, multispectral, and automated descent loading, depending connected circumstantial requirements. One of our astir precocious image study platforms is StrataQuest, which includes modules for single-cell analysis, multicellular building detection, vicinity analysis, and more. Researchers tin create and prevention civilization study workflows and reuse information for early studies.

To illustrate, successful 1 illustration involving colon insubstantial stained pinch respective immune markers, nuclei are detected utilizing DAPI staining, followed by immune compartment phenotyping and colon crypt detection. A region representation is past generated, which supports vicinity analysis—examining nan spatial proximity of immune cells to epithelial structures. This type of study yields captious insights into some compartment personality and spatial organization.

In nan latest type of our software, we person integrated precocious visualization and information mentation tools, including 3D diagrams, violin plots, and manifold learning techniques specified arsenic SONG, UMAP, and t-SNE plots—all accessible straight wrong nan platform.

Looking ahead, we are preparing to motorboat Colubris adjacent year, an all-in-one acquisition and study system. Colubris will characteristic real-time AI-assisted image study and information mining, and is specifically engineered to grip high-volume data, delivering broad solutions for modern biomedical imaging needs.

About Prof. Diana Mechtcheriakova

Assoc. Prof. Diana Mechtcheriakova is nan caput of nan investigation group Molecular Systems Biology and Pathophysiology astatine nan Medical University of Vienna. Her investigation interests see improvement of systems biology approaches, AI-powered solutions, pinch awesome attraction connected B-cell biology, immuno-oncology, lymphoid structures successful immunity and crab pinch translational perspectives.

About TissueGnostics

TissueGnostics (TG) is an Austrian institution focusing connected integrated solutions for precocious contented and/or precocious throughput scanning and study of biomedical, veterinary, earthy sciences, and method microscopy samples.

TG has been founded by scientists from nan Vienna University Hospital (AKH) successful 2003. It is now a globally progressive institution pinch subsidiaries successful nan EU, nan USA, and China, and customers successful 30 countries.

TissueGnostics portfolio

TG scanning systems are presently based connected versatile automated microscopy systems pinch aliases without image study capabilities. We strive to supply cutting-edge exertion solutions, specified arsenic multispectral imaging and context-based image study arsenic good arsenic established features for illustration Z-Stacking and Extended Focus. This is mixed pinch a beardown accent connected automation, easiness of usage of each solutions, and nan accumulation of publication-ready data.

The TG systems connection integrated workflows, i.e. scan and analysis, for integer slides aliases images of insubstantial sections, Tissue Microarrays (TMA), compartment civilization monolayers, smears, and different samples connected slides and oversized slides, successful Microtiter plates, Petri dishes and specialized sample containers. TG besides provides dedicated workflows for FISH, CISH, and different dot structures.

TG study package isolated from being integrated into afloat systems is afloat standalone tin and supports a wide assortment of scanner image formats arsenic good arsenic integer images taken pinch immoderate microscope.