Dr Pimenta on Novel Approaches to Evaluate Tumor Progression and Immune Evasion in Soft Tissue Sarcomas

"This study has opened up many novel areas of research in liposarcoma, beyond the [epigenetic dysregulation] study in dedifferentiated liposarcoma."

Erica Maria Pimenta, MD, PhD, a clinical fellow in medicine at Brigham and Women's Hospitalmedical oncologist and translational researcher, discussed the implications of recent findings on epigenetic dysregulation in dedifferentiated liposarcoma (DDLPS), with a particular focus on the IGF1/PPARG2 signaling axis and ELF1 transcriptional activity.

The study, she noted, lays may set the foundation for a broader research agenda aimed at understanding non-genetic mechanisms of tumor progression and immune evasion in soft tissue sarcomas.

Historically, therapeutic research in liposarcoma has focused on genomic alterations such as MDM2 and CDK4 amplification. However, new transcriptomic analyses have identified ELF1 activation as a predominant feature in DDLPS, suggesting a key role in maintaining the dedifferentiated phenotype. Current investigations are evaluating the molecular pathways downstream of ELF1, including its potential influence on proliferative signaling and lineage plasticity. Given that ELF1 agonists are already available and widely used in other contexts, these findings offer a potential path toward therapeutic repurposing in sarcoma.

In addition to transcriptional regulation, the study also explored how dedifferentiation impacts the immune microenvironment. Pimenta noted that macrophages are the dominant immune cell type in the DDLPS tumor microenvironment. Ongoing research is examining how interactions between tumor cells and macrophages contribute to immune escape and whether these interactions could be modulated therapeutically. This line of inquiry is particularly relevant as immune checkpoint inhibition has shown limited efficacy in soft tissue sarcoma, and strategies to enhance antitumor immunity remain a critical unmet need.