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14 Publications visible to you, out of a total of 14
Transcriptomic profiling identifies immunotherapy-responsive phenotypes in microsatellite-stable metastatic colorectal cancer.

Abstract (Expand)

Conventional immune checkpoint inhibitors (ICIs) remain largely ineffective in microsatellite-stable metastatic colorectal cancer (MSS mCRC), where low tumor immunogenicity and molecular heterogeneity … across metastatic sites underpin therapeutic resistance. We present a comprehensive transcriptomics analysis of metastatic and primary tumor biopsies from MSS mCRC patients treated with botensilimab (BOT; Fc-enhanced anti-CTLA-4) +/- balstilimab (BAL; anti-PD-1). Self-organizing map (SOM) machine learning stratified tumors into four molecular types, including a liver-like (LIV) subtype characterized by metabolic reprogramming and immunosuppressive signatures, and proliferative (PRO), inflammatory (INF), and mesenchymal (MES) types concordant with pan-cancer classifications. PRO, INF, and MES types were enriched for epithelial tumor cells, immune cells, and fibroblasts, respectively, defining immune-depleted, immune-enriched, and fibrotic states along a plasticity gradient. We observed treatment-related transcriptomic shifts toward immune-enriched states via upregulation of antigen presentation, T cell recruitment, and cytotoxicity pathways. INF and MES tumor types exhibited improved clinical responses and survival vs PRO and LIV types. This study identified distinct tumor microenvironment states that align along an immunophenotype axis marked by CD74, interferon-gamma, and APOBEC3 expression identified previously for primary CRC. Our findings provide novel insights into molecular correlates of immunotherapy response in MSS mCRC, potentially informing future therapeutic strategies to expand ICI efficacy to historically unresponsive tumors.

Authors: T. Konecny, N. Zadirako, A. Grigoryan, M. Tamazyan, S. Mnatsakanyan, L. Stepanyan, H. Loeffler-Wirth, S. Bourdelais, G. Mednick, C. Delepine, D. Chand, H. Binder

Date Published: 16th Jun 2026

Publication Type: Journal

Reprogramming of stroma-derived chemokine networks drives the loss of tissue organization in nodal B cell lymphoma.

Abstract (Expand)

Lymph node (LN) function requires the organization of cells into higher-order spatial units. However, the principles governing LN architecture in health and disease remain poorly understood. Here, we … used single-cell and spatial mapping to investigate the mechanisms directing immune cell organization in human LNs and its disruption in architecturally distinct lymphoma entities: indolent follicular lymphoma (FL) and aggressive diffuse large B cell lymphoma (DLBCL). Our data substantiate the central role of LN-resident stromal cells in chemokine-driven lymphocyte zonation and reveal an inflammatory feedback loop fueled by tumor-reactive T cells that triggers stromal remodeling, progressive loss of homeostatic chemokine gradients, and tissue disorganization from a non-malignant state to FL and DLBCL. Loss of homeostatic chemokines was associated with adverse patient survival, identifying the underlying architectural rearrangement as a key event during lymphomagenesis. Collectively, our results highlight the principles of LN organization and suggest how lymphoma-induced microenvironmental reprogramming drives the loss of tissue organization.

Authors: F. Czernilofsky, A. Mathioudaki, L. Jopp-Saile, R. Lutz, D. Vonficht, X. Wang, C. Schniederjohann, H. Voehringer, T. Roider, M. A. Baertsch, C. Rodemer, H. Loffler-Wirth, M. Grau, D. Fitzgerald, J. Mammen, J. Kosla, N. Liebers, P. M. Bruch, D. Ordonez-Rueda, A. Brobeil, G. Mechtersheimer, C. Pabst, C. Muller-Tidow, A. Trumpp, M. Seifert, F. Neumann, M. Heikenwalder, V. Benes, W. Huber, J. Distler, G. Lenz, H. Binder, R. Siebert, G. P. Nolan, M. Gerstung, J. B. Zaugg, D. Hubschmann, S. Haas, S. Dietrich

Date Published: 31st Mar 2026

Publication Type: Journal

Spatial transcriptome analysis of the human eyelid depicts meibomian gland cell differentiation: A pilot study.

Abstract (Expand)

Meibomian glands (MGs) are an integral component of the ocular defense system, as their secretion product, meibum, is essential for protecting the eye surface. To characterize the transcriptional program … underlying meibum production, we employed spatial transcriptomics (ST) analysis of the human eyelid from a sample from a 60-year-old male. We resolved 18 distinct eyelid clusters, representing structures such as the conjunctiva, epidermis, hair-associated sebaceous glands, and MGs. Focusing on the MG, we distinguished basal (MEI-B cluster) and differentiating (MEI-DIFF cluster) meibocytes, as well as a third, duct-related cluster (MEI-DUCT). Self-organizing maps (SOM) portrayal of ST images and pseudotime analysis confirmed progress from MEI-B to MEI-DIFF and further to MEI-DUCT, as the latter turned out to include terminally differentiated meibocytes. Accordingly, gene set enrichment analysis associated early/intermediate meibocyte maturation with energy and lipid metabolism, and later stages with barrier functions. We also identified significant differences between the MG and sebaceous gland transcriptomes. The MG-specific signature included transcripts such as AQP9, MMP3, and PITX1, and selective expression of PITX1 in the MG compared to the sebaceous gland was confirmed by immunohistochemistry on the same sample and samples from three other elderly adults. We deliver the first spatial portrait of the human MG transcriptional landscape. Besides enhancing our understanding of MG physiology, our study identifies novel targets for regulating MG homeostasis in health and disease.

Authors: H. Binder, U. Hampel, H. Loeffler-Wirth, F. Hansmann, H. Pfannkuche, M. Schmidt, M. R. Schneider

Date Published: 19th Sep 2025

Publication Type: Journal

Single-cell transcriptomics and epigenomics point to CD58-CD2 interaction in controlling primary melanoma growth and immunity.

Abstract

Not specified

Authors: A. Stubenvoll, M. Schmidt, J. Moeller, M. A. L. Chango, C. Schultz, O. Antoniadou, H. Loeffler-Wirth, S. Bernhart, F. Grosse, B. Thier, A. Paschen, U. Anderegg, J. C. Simon, M. Ziemer, C. T. Schoeder, H. Binder, M. Kunz

Date Published: 15th Jan 2025

Publication Type: Journal

Transcriptional states of CAR-T infusion relate to neurotoxicity – lessons from high-resolution single-cell SOM expression portraying

Abstract (Expand)

Anti-CD19 CAR-T cell immunotherapy is a hopeful treatment option for patients with B cell lymphomas, however it copes with partly severe adverse effects like neurotoxicity. Single-cell resolved molecular … data sets in combination with clinical parametrization allow for comprehensive characterization of cellular subpopulations, their transcriptomic states, and their relation to the adverse effects. We here present a re-analysis of single-cell RNA sequencing data of 24 patients comprising more than 130,000 cells with focus on cellular states and their association to immune cell related neurotoxicity. For this, we developed a single-cell data portraying workflow to disentangle the transcriptional state space with single-cell resolution and its analysis in terms of modularly-composed cellular programs. We demonstrated capabilities of single-cell data portraying to disentangle transcriptional states using intuitive visualization, functional mining, molecular cell stratification, and variability analyses. Our analysis revealed that the T cell composition of the patient's infusion product as well as the spectrum of their transcriptional states of cells derived from patients with low ICANS grade do not markedly differ from those of cells from high ICANS patients, while the relative abundancies, particularly that of cycling cells, of LAG3-mediated exhaustion and of CAR positive cells, vary. Our study provides molecular details of the transcriptomic landscape with possible impact to overcome neurotoxicity. Keywords: CAR-T cell immunotherapy; bioinformatics workflow; data portraying; single-cell transcriptomics; transcriptional states. Copyright © 2022 Loeffler-Wirth, Rade, Arakelyan, Kreuz, Loeffler, Koehl, Reiche and Binder.

Authors: Henry Loeffler-Wirth, Michael Rade, Arsen Arakelyan, Markus Kreuz, Markus Loeffler, Ulrike Koehl, Kristin Reiche, Hans Binder

Date Published: 28th Sep 2022

Publication Type: Journal

The Evolving Faces of the SARS-CoV-2 Genome

Abstract (Expand)

Surveillance of the evolving SARS-CoV-2 genome combined with epidemiological monitoring and emerging vaccination became paramount tasks to control the pandemic which is rapidly changing in time and … space. Genomic surveillance must combine generation and sharing sequence data with appropriate bioinformatics monitoring and analysis methods. We applied molecular portrayal using self-organizing maps machine learning (SOM portrayal) to characterize the diversity of the virus genomes, their mutual relatedness and development since the beginning of the pandemic. The genetic landscape obtained visualizes the relevant mutations in a lineage-specific fashion and provides developmental paths in genetic state space from early lineages towards the variants of concern alpha, beta, gamma and delta. The different genes of the virus have specific footprints in the landscape reflecting their biological impact. SOM portrayal provides a novel option for ‘bioinformatics surveillance’ of the pandemic, with strong odds regarding visualization, intuitive perception and ‘personalization’ of the mutational patterns of the virus genomes.

Authors: Maria Schmidt, Mamoona Arshad, Stephan H. Bernhart, Siras Hakobyan, Arsen Arakelyan, Henry Loeffler-Wirth, Hans Binder

Date Published: 3rd Sep 2021

Publication Type: Journal

A Transcriptome-Wide Isoform Landscape of Melanocytic Nevi and Primary Melanomas Identifies Gene Isoforms Associated with Malignancy.

Abstract (Expand)

Genetic splice variants have become of central interest in recent years, as they play an important role in different cancers. Little is known about splice variants in melanoma. Here, we analyzed a … genome-wide transcriptomic dataset of benign melanocytic nevi and primary melanomas (<i>n</i> = 80) for the expression of specific splice variants. Using kallisto, a map for differentially expressed splice variants in melanoma vs. benign melanocytic nevi was generated. Among the top genes with differentially expressed splice variants were Ras-related in brain 6B (<i>RAB6B</i>), a member of the RAS family of GTPases, Macrophage Scavenger Receptor 1 (<i>MSR1</i>), Collagen Type XI Alpha 2 Chain (<i>COLL11A2</i>), and LY6/PLAUR Domain Containing 1 (<i>LYPD1</i>). The Gene Ontology terms of differentially expressed splice variants showed no enrichment for functional gene sets of melanoma vs. nevus lesions, but between type 1 (pigmentation type) and type 2 (immune response type) melanocytic lesions. A number of genes such as Checkpoint Kinase 1 (<i>CHEK1</i>) showed an association of mutational patterns and occurrence of splice variants in melanoma. Moreover, mutations in genes of the splicing machinery were common in both benign nevi and melanomas, suggesting a common mechanism starting early in melanoma development. Mutations in some of these genes of the splicing machinery, such as Serine and Arginine Rich Splicing Factor A3 and B3 (<i>SF3A3</i>, <i>SF3B3</i>), were significantly enriched in melanomas as compared to benign nevi. Taken together, a map of splice variants in melanoma is presented that shows a multitude of differentially expressed splice genes between benign nevi and primary melanomas. The underlying mechanisms may involve mutations in genes of the splicing machinery.

Authors: Siras Hakobyan, Henry Loeffler-Wirth, Arsen Arakelyan, Hans Binder, Manfred Kunz

Date Published: 2nd Jul 2021

Publication Type: Journal

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