Banfi, C. | Search bioRxiv

bioRxiv2026

Active Surveillance Reveals a Systemic Pro-Resolving Th2 Immune Program Linked to 1 Desmoid Tumor Regression

Desmoid fibromatosis (DF) is a rare mesenchymal neoplasm with an unpredictable clinical course, where spontaneous regression or progression occurs in a significant subset of patients through largely undefined mechanisms. The use of active surveillance (AS) offers the opportunity to investigate whether tumor- or host-driven systemic and local immune features may explain these divergent outcomes, improving patient management. A prospective observational study enrolled 55 patients with primary sporadic DF managed with AS. Clinical evolution was categorized as progression, regression, or stable disease according to RECIST 1.1. Immunomonitoring with multicolor flow cytometry identified distinct systemic T-helper polarization states stratifying clinical trajectories: regressors showed a Th2-skewed profile, while progressors displayed activated T-helper cells and Th1/Th9/Th17 subsets. Higher baseline Th2 levels associated with regression and longer progression-free survival. Plasma proteomic and whole-blood transcriptomic analyses confirmed coordinated IL-4/IL-13-linked pro-resolving programs in regressors and inflammatory, early T-cell activation signatures in progressors. Tumor transcriptomics revealed adaptive, antigen-presentation and restrained immune programs in regressing lesions versus innate inflammatory, interferon and TGF-{beta}-driven fibrotic pathways in progressing tumors. These findings identify systemic T-helper polarization as a biomarker of DF behavior and highlight coordinated systemic-tumoral immune programs underlying clinical outcomes, supporting more precise clinical management.

immunology↗

bioRxiv2025

ARABIDOPSIS Bsister and SEEDSTICK MADS-box transcription factors modulate maternal nutrient flow for seed development in Arabidopsis

Successful seed development in angiosperms depends on the coordinated transport and allocation of sugars from maternal tissues to the developing embryo and endosperm. In Arabidopsis thaliana, ovules function as carbohydrate sink organs, accumulating starch in both gametophytic and sporophytic domains prior to fertilization. This stored starch is later mobilized to support early embryogenesis. Despite extensive knowledge of starch metabolism in photosynthetic tissues, the regulatory mechanisms governing sugar transport in reproductive organs remain poorly understood. Recent studies have identified fertilization-dependent changes in nutrient flow, including callose-mediated modulation of symplastic transport at the phloem unloading site. However, the molecular players orchestrating these transitions are largely unknown. Here, we show that the MIKC MADS domain transcription factors ABS/TT16 and STK play critical roles in regulating maternal nutrient flow during ovule maturation and seed development. We dissect their functional redundancy using omics and genetic approaches, underscoring the importance of different ovule tissues in coordinating sugar transport pathways for post-fertilization development. Our findings reveal a previously underappreciated layer of genetic control over nutrient allocation in reproductive tissues and provide new insights into the metabolic reprogramming required for successful seed formation.

plant biology↗