A5064279273- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Immune Cell Function and Interaction
- Bladder and Urothelial Cancer Treatments
- Radiomics and Machine Learning in Medical Imaging
- Single-cell and spatial transcriptomics
- Prostate Cancer Treatment and Research
- Molecular Biology Techniques and Applications
- Cancer Research and Treatments
- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
- Cell Image Analysis Techniques
- Prostate Cancer Diagnosis and Treatment
- Genetic factors in colorectal cancer
- Monoclonal and Polyclonal Antibodies Research
- Cancer, Lipids, and Metabolism
- Peptidase Inhibition and Analysis
- Cancer Cells and Metastasis
- Chemokine receptors and signaling
- vaccines and immunoinformatics approaches
- Nanoplatforms for cancer theranostics
- RNA modifications and cancer
- Virus-based gene therapy research
- Ferroptosis and cancer prognosis
University Medical Center Hamburg-Eppendorf
2018-2025
Universität Hamburg
2018-2025
University of North Carolina at Chapel Hill
2022
University of Nebraska Medical Center
2022
VA Western New York Healthcare System
2022
TIGIT is an inhibitory immune checkpoint receptor and a putative target for novel therapies. Here, we analysed two different types of tissue microarrays healthy lymphatic various inflamed tissues, colorectal lung cancers, as well >1700 tumour samples from 86 entities and/or PD-1 by bright field multiplex fluorescence immunohistochemistry. was detected in CD8 + cytotoxic T cells, CD4 helper FOXP3 regulatory NK but not CD11c dendritic CD68 macrophages, CD20 B lymphocytes. expression...
Expansion of CD8+ cytotoxic Tlymphocytes is a prerequisite for anti-cancer immune activity and has gained interest in the era checkpoint therapy.To understand T cell dynamics tumor microenvironment, we used multiplex fluorescence immunohistochemistry to quantitate proliferation (Ki67 co-expression) tissue microarrays from 1107 colorectal, 642 renal cell, 1066 breast, 375 ovarian, 451 pancreatic 347 gastric cancer samples.The density percentage proliferating (Ki67+) cells were both highly...
The Ki-67 labeling index (Ki-67 LI) is a strong prognostic marker in prostate cancer, although its analysis requires cumbersome manual quantification of immunostaining 200-500 tumor cells. To enable automated LI assessment routine clinical practice, framework for quantification, which comprises three different artificial intelligence steps and an algorithm cell-distance multiplex fluorescence immunohistochemistry (mfIHC) staining, was developed validated cohort 12,475 cancers. impact the...
Hodgkin's lymphoma (HL) is characterized by a high background of inflammatory cells which play an important role for the pathogenesis disease. T cell immunoreceptor with Ig and ITIM domains (TIGIT) inhibitory immune checkpoint receptor putative target novel immunotherapies. To study patterns TIGIT expression in surrounding malignant including Hodgkin cells, Reed-Sternberg histiocytic microenvironment (ME) tissue microarray (TMA) was constructed from punches measuring 2 mm diameter obtained...
Programmed death ligand 1 (PD-L1) is the target of immune checkpoint inhibitor therapies in a growing number tumor types, but unanimous picture on PD-L1 expression across cancer types lacking.We analyzed immunohistochemical 11,838 samples from 118 human and its relationship with infiltrating CD8 positive lymphocytes.At cut-off level 10% cells, positivity was seen 85 (72%) including thymoma (100% positive), Hodgkin's lymphoma (93%), anaplastic thyroid carcinoma (76%), Kaposi sarcoma (71%),...
Quantity and the spatial relationship of specific immune cell types can provide prognostic information in bladder cancer. The objective study was to characterize interplay role different subpopulations
Abstract Microsatellite instability is a strong predictor of response to immune checkpoint therapy and patient outcome in colorectal cancer. Although enrichment distinct T‐cell subpopulations has been determined impact the outcome, little known about underlying changes composition tumor microenvironment. To assess density, composition, degree functional marker expression, spatial interplay subpopulations, 79 microsatellite instable (MSI) 1,045 stable (MSS) cancers were analyzed. A tissue...
Immune checkpoint inhibitors have recently been approved by the US FDA as first and/or second line therapy in a subset of cancer types. Recent evidence suggests that quantity tumor infiltrating lymphocytes (TILs) influences likelihood response to immune inhibitors. Here, we set out assess density CD8+ wide range different types and subtypes.The was compared across using tissue microarrays (TMAs) composed up 50 samples each from 84 subtypes. In total 2652 cancers 608 normal tissues were...
Microsatellite instability (MSI) has emerged as a predictive biomarker for immune checkpoint inhibitor therapy. Cancer heterogeneity represents potential obstacle the analysis of predicitive biomarkers. MSI been reported in pancreatic cancer, but data on possible extent intratumoral are lacking.To study tissue microarray (TMA) comprising 597 tumors was screened by immunohistochemistry with antibodies mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6.In six suspicious cases, large...
Focal T lymphocyte aggregates commonly occur in colorectal cancer; however, their biological significance is unknown. To study focal of lymphocytes, a deep learning-based framework for automated identification cell accumulations (T nests) was developed using CD8, PD-1, CD112R, and Ki67 multiplex fluorescence immunohistochemistry. evaluate the clinical these parameters, cohort 523 cancers with follow-up data analyzed. Spatial analysis locally enriched CD8+ density cell-to-cell contacts...
Abstract Multiplex fluorescence IHC (mfIHC) approaches were yet either limited to six markers or a small tissue size that hampers translational studies on large microarray cohorts. Here we have developed BLEACH&STAIN mfIHC method enabled the simultaneous analysis of 15 biomarkers (PD-L1, PD-1, CTLA-4, panCK, CD68, CD163, CD11c, iNOS, CD3, CD8, CD4, FOXP3, CD20, Ki67, and CD31) in 3,098 tumor samples from 44 different carcinoma entities within one week. To facilitate automated immune...
Abstract Purpose Enhancer of zeste homolog 2 (EZH2), the catalytic part Polycomb repressive complex (PRC2), has a prognostic role in renal cell carcinoma (RCC) and was recently shown to modulate immune response by reducing tumor immunogenicity. Methods To investigate whether EZH2 might be driven modified environment, more than 1800 RCCs were analyzed tissue microarray for expression CD8 positive lymphocytes quantitated automated digital imaging. Results positivity found 75.2% 1603...
SAM pointed domain-containing Ets transcription factor (SPDEF), a member of the ETS family, has been associated with prostate cancer development; however, its role in tumour development and progression is controversial. In present study, SPDEF expression was analysed on tissue microarray >12,000 samples. levels were higher most samples than normal epithelium, suggesting upregulated cancer. Nuclear identified 80% samples, considered weak 26.4%, moderate 40.1% strong 13.5% cases. positivity...
Small-cell cancer of the urinary bladder is a rare but highly aggressive disease. It currently unclear whether immune checkpoint therapies that have been approved for urothelial carcinomas will also be efficient in small-cell carcinomas. In this study, we analyzed potential predictors response including PD-L1 expression and quantity location tumor-infiltrating lymphocytes (TILs) 12 69 "classical" cancers by immunohistochemistry. The analysis revealed were characterized virtual absence an...
CTLA-4 is an inhibitory immune checkpoint receptor and a negative regulator of anti-tumor T-cell function. This study aimed for comparative analysis CTLA-4+ cells between different tumor entities. To quantify cells, 4582 samples from 90 entities as well 608 76 normal tissue types were analyzed by immunohistochemistry in microarray format. Two antibody clones (MSVA-152R CAL49) validated quantified using deep learning framework automated exclusion unspecific immunostaining. Comparing both...
A characteristic feature of testicular seminoma is the abundance immune cells in tumor microenvironment, raising possibility that checkpoint inhibitors may serve as a therapeutic option these types tumors. T cell immunoreceptor with Ig and ITIM domains (TIGIT) an inhibitory receptor analogy to PD-1, drugs targeting TIGIT are currently being investigated clinical trials. Little known about expression proteins seminomas. Therefore present study performed immunohistochemical analysis determine...
Abstract Survivin is an inhibitor of apoptosis. Aberrant survivin expression occurs in malignant tumors and has often been linked to unfavorable patient outcome. Here we analyzed 12 432 prostate cancers by immunohistochemistry. immunostaining was regularly expressed at high levels normal epithelium but reduced cancers. Among 9492 evaluable cancers, 9% strongly, 19% moderately, 28% weakly, 44% lacked it. Loss cytoplasmic seen advanced tumor stage, higher Gleason score, preoperative PSA...
Background: Although quantification of tumor infiltrating lymphocytes (TILs) has become increasing interest in immuno-oncology, only little is known about TILs infiltration the microenvironment and its predictive value vulvar cancer. Methods: Immunohistochemistry automated digital image analysis was applied to measure densities CD3+ (DAKO, #IR503) CD8+ #IR623) at invasive margin center 530 squamous cell cancers. Results: An elevated density T-cell significantly associated with low stage (p =...
Aging | doi:10.18632/aging.203113. Niclas C. Blessin, Raed Abu-Hashem, Tim Mandelkow, Wenchao Li, Ronald Simon, Claudia Hube-Magg, Christina Möller-Koop, Melanie Witt, Alice Schmidt, Franziska Büscheck, Christoph Fraune, Andreas M. Luebke, Katharina Möller, Frank Jacobsen, Florian Lutz, Maximilian Lennartz, Stefan Steurer, Guido Sauter, Doris Höflmayer, Maria Tsourlakis, Andrea Hinsch, Eike Burandt, Waldemar Wilczak, Sarah Minner, Till S. Clauditz
Background: Remodelling and spacing factor 1 (RSF1) is involved in the regulation of chromatin remodelling represents a potential therapeutic target. High RSF1 expression has been linked to adverse tumour features many cancer types, but its role prostate uncertain.Methods: In this study, was analysed by immunohistochemistry on tissue microarray with 17,747 cancers.Results: Nuclear staining 16,456 interpetable cancers considered strong, moderate, weak negative 25.2%, 48.7%, 5.3% 20.8%...
Evidence suggests that the quantity of cytotoxic lymphocytes influences likelihood for a successful application immune checkpoint inhibitors. To compare density CD8+lymphocytes across various different tumor types, tissue microarray (TMA) composed up to 50 samples each from 85 cancer types and subtypes was analyzed. A total 2652 cancers 608 normal tissues were successfully analyzed by CD8 immunohistochemistry followed automated image analysis digitized slides. The median number ranged 6...
Trophoblast cell surface antigen 2 (TROP2; EpCAM2) is a transmembrane glycoprotein which closely related to EpCAM (EpCAM; EpCAM1). Both proteins share partial overlapping functions in epithelial development and expression but have not been comparatively analyzed together bladder carcinomas. TROP2 constitutes the target for antibody-drug conjugate Sacituzumab govitecan (SG; TrodelvyTM) has approved treatment of metastatic urothelial carcinoma by United States Food Drug administration (FDA)...
Abstract Background: Microsatellite instability (MSI-h) is a strong biomarker to predict response immune checkpoint therapy and patient’s outcome in colorectal cancer. Although enrichment of distinct T-cell subpopulations, such as type 1 cytotoxic T-cells (Tc1) or helper (Th1), have been identified impact therapy, only little known about the underlying changes composition tumor microenvironment. Material Methods: To assess density, composition, degree functional marker expression, spatial...
Abstract Background: Although there is raising evidence that the density and level of immune checkpoint expression cell subpopulations are in direct contact to tumor cells (intraepithelial) can predict response therapy patient’s outcome, a comprehensive assessment intraepithelial their spatial interplay lacking. Material methods: To comprehensively assess density, expression, 48 expressing leukocyte 46 carcinoma entities, 4740 samples tissue microarray format were stained with 21 antibodies...
Abstract KDM6A, also known as UTX (ubiquitously transcribed X chromosome tetratricopeptide repeat protein) is an epigenetic regulator which frequently mutated in urothelial carcinoma. Because KDM6A loss causes a dependency on EZH2, potential therapeutic target, analysis may have importance. Most data mutations are derived from next generation sequencing (NGS). However, because of the combination high rate truncating mutations, localization Xp11.3, and male predominance bladder cancer, many...