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Updated: May 14, 2026
A Mouse Model of Incompletely Resected Soft Tissue Sarcoma for Testing (Neo)adjuvant Therapies
Published on: July 28, 2020
Prognostic Value of Regnase-1 in High-Grade Soft Tissue Sarcoma: Favourable in UPS, Yet Inverted in Adjuvantly
Julie Zangarini1, Axel Künstner2, Florian Lenz3
1Clinic for Hematology and Oncology, University Hospital Schleswig-Holstein Campus Lübeck, 23562 Lübeck, Germany.
Background:
High-grade soft tissue sarcomas (STSs) are heterogeneous tumours lacking robust prognostic or predictive biomarkers. Regnase-1, an immune RNase, enhances antitumour immunity by limiting immunosuppressive tumour microenvironment (TME) components (e.g., myeloid-derived suppressor cells (MDSCs)), but remains unexplored in STS. As CD68+ tumour-associated macrophages (TAMs) drive TME suppression and poor prognosis in non-translocation-driven STS, we evaluated Regnase-1 and CD68+ TAMs to assess Regnase-1 as an indicator of an immunologically activated TME.
Methods:
Immunohistochemistry scoring of Regnase-1 and CD68+ TAMs was performed in 91 patients. Overall survival (OS) was assessed by Kaplan-Meier and Cox regression, and findings were validated in an independent "The Cancer Genome Atlas" Sarcoma (TCGA-SARC) cohort (n = 212).
Results:
In UPS, Regnase-1-high predicted longer OS (17.0 months vs. not reached; p = 0.0247) and lower mortality (univariate hazard ratio (HR) = 0.3; p = 0.0343; multivariate HR = 0.4; p = 0.0413), but not after radiotherapy. CD68+ TAM-high predicted shorter OS (13.0 months vs. not reached; p = 0.0274) and higher mortality (HR = 2.0, 95% CI 1.1-3.7; p = 0.0325). Both Regnase-1 effects were reproduced in TCGA-SARC. Regnase-1-high tumours showed inflammatory/interferon enrichment, reduced TGF-β signalling, and SERPINE1 upregulation.
Conclusions:
Regnase-1 marked a pro-inflammatory TME and favourable outcome in UPS, but this effect may reverse upon radiotherapy.
