IFN-α plus anti-PD-1 therapy enhanced tumor control in a xenograft model, and a five-marker IHC panel showed a trend in predicting outcomes for ICB-treated liposarcoma patients.
IFN-α treatment enhances anti-PD-1 efficacy in preclinical models of well-/dedifferentiated liposarcoma, providing proof-of-concept for combination therapy.
Well-/dedifferentiated liposarcoma is characterized by frequent local recurrence and limited responsiveness to immune checkpoint blockade (ICB), highlighting the need for pathology-feasible immune stratification and rational combination strategies. We integrated bulk transcriptomics, single-cell RNA sequencing, proteomics, and spatial immunofluorescence to characterize the tumor immune microenvironment in WD/DD LPS. Unsupervised analyses identified two reproducible states: an immune-high (Hi) subtype enriched for type I interferon programs and an immune-low (Lo) subtype enriched for extracellular matrix (ECM)-associated features. Based on these signatures, we derived a five-marker immunohistochemistry (IHC) panel (CD8A, CD27, AOAH, NCF1, and LST1) to enable pathology-based immune subtyping. In a small, independent exploratory cohort of ICB-treated WD/DD LPS patients ( n = 10), the locked classifier showed a directionally consistent trend in outcomes, but was underpowered and should be considered hypothesis-generating, warranting validation in larger, prospectively collected cohorts. IFN-α downregulated tumor-cell-derived COL6A1 in vitro and was associated with reduced ECM-linked exclusion features. In a PBMC-humanized xenograft model, IFN-α plus anti-PD-1 therapy enhanced tumor control, accompanied by increased CD8 + T-cell infiltration, providing preclinical proof-of-concept support for IFN-α as a combination partner for PD-1 blockade. Mechanistically, the proposed COL6 axis is a hypothesis supported by in vitro IFN-α-dependent suppression of tumor cell COL6A1 and correlative multi-omic/spatial observations; the in vivo model used here does not establish COL6 causality, and definitive testing will require genetic loss-of-function studies. Together, these findings define an immune-ECM axis, present a pathology-ready IHC framework for hypothesis-generating immune stratification, and support further investigation of IFN-α-based combination strategies under rigorous clinical validation.
Zhuang et al. (Wed,) conducted a other in Well-/dedifferentiated liposarcoma (n=10). IFN-α plus anti-PD-1 therapy / 5-marker IHC panel was evaluated on Tumor control and clinical outcomes. IFN-α plus anti-PD-1 therapy enhanced tumor control in a xenograft model, and a five-marker IHC panel showed a trend in predicting outcomes for ICB-treated liposarcoma patients.