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4 Publications visible to you, out of a total of 4
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

Integrated analysis of the blood metallome and DNA methylation, gene expression, and protein levels of immune-associated genes in residents from mining region

Abstract (Expand)

Environmental exposure to toxic and essential metals can disrupt host immune function through mechanisms involving epigenetic, transcriptional, and post-transcriptional regulation. Although numerous … studies have investigated these regulatory layers separately, integrative analyses across molecular levels in relation to metallome is missing. In this study, we performed a targeted multi-omics analysis of six immune-associated genes (NFKB1, CDKN2A, IGF2, H19, ESR1, and APOA5) and corresponding proteins in healthy residents from a long-term mining region (MRR, n = 46) and a non-mining region (NMR, n = 48). Transcriptome data were generated by mRNA sequencing, while DNA methylation data were obtained using targeted bisulfite sequencing by analyzing previously identified differentially methylated positions. Plasma protein levels were measured by enzyme-linked immunosorbent assay, and plasma metal concentrations were quantified using inductively coupled plasma mass spectrometry. We observed significantly higher plasma levels of NFKB1 and CDKN2A proteins, along with lower ESR1 transcript levels, in residents of the mining region compared to the non-mining region. NFKB1 protein levels were associated with both promoter methylation and residence in mining region, suggesting a regulatory cascade from DNA methylation to protein expression. IGF2 protein levels were higher in males and showed positive associations with age and the cumulative Z-score of essential metal mixture burden. Our results show that long-term residence in mining regions is associated with changes in NFKB1 at both the DNA methylation and protein levels, which may serve as a sensitive biomarker of metal exposure.

Authors: Yeva Bareghamyan, Arpine Minasyan, Suren Davitavyan, Anna Petrackova, Jakub Savara, Romana Nesnadna, Eva Kriegova, Jonathan Schug, Arsen Arakelyan, Ani Stepanyan

Date Published: 4th Jan 2026

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

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