CD4+ T cell and M2 macrophage infiltration predict dedifferentiated liposarcoma patient outcomes
Brett A Schroeder1,2, Natalie A LaFranzo3, Bonnie J LaFleur4
1National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Background:
Dedifferentiated liposarcoma (DDLPS) is one of the most common soft tissue sarcoma subtypes and is devastating in the advanced/metastatic stage. Despite the observation of clinical responses to PD-1 inhibitors, little is known about the immune microenvironment in relation to patient prognosis.
Methods:
We performed a retrospective study of 61 patients with DDLPS. We completed deep sequencing of the T-cell receptor (TCR) β-chain and RNA sequencing for predictive modeling, evaluating both immune markers and tumor escape genes. Hierarchical clustering and recursive partitioning were employed to elucidate relationships of cellular infiltrates within the tumor microenvironment, while an immune score for single markers was created as a predictive tool.
Results:
Although many DDLPS samples had low TCR clonality, high TCR clonality combined with low T-cell fraction predicted lower 3-year overall survival (p=0.05). Higher levels of CD14+ monocytes (p=0.02) inversely correlated with 3-year recurrence-free survival (RFS), while CD4+ T-cell infiltration (p=0.05) was associated with a higher RFS. Genes associated with longer RFS included PD-1 (p=0.003), ICOS (p=0.006), BTLA (p=0.033), and CTLA4 (p=0.02). In a composite immune score, CD4+ T cells had the strongest positive predictive value, while CD14+ monocytes and M2 macrophages had the strongest negative predictive values.
Conclusions:
Immune cell infiltration predicts clinical outcome in DDLPS, with CD4+ cells associated with better outcomes; CD14+ cells and M2 macrophages are associated with worse outcomes. Future checkpoint inhibitor studies in DDLPS should incorporate immunosequencing and gene expression profiling techniques that can generate immune landscape profiles.
Insights
Immune cell infiltration impacts dedifferentiated liposarcoma outcomes. CD4+ T-cells correlate with better survival, while CD14+ monocytes and M2 macrophages indicate worse prognosis in soft tissue sarcoma.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Dedifferentiated liposarcoma (DDLPS) is a common, aggressive soft tissue sarcoma.
- Advanced DDLPS has a poor prognosis, despite observed responses to PD-1 inhibitors.
- The immune microenvironment's role in DDLPS prognosis remains poorly understood.
Purpose of the Study:
- To investigate the relationship between immune cell infiltration and patient prognosis in DDLPS.
- To identify immune markers and tumor escape genes predictive of DDLPS outcomes.
- To develop a predictive immune score for DDLPS.
Main Methods:
- Retrospective analysis of 61 DDLPS patients.
- Deep sequencing of T-cell receptor (TCR) β-chain and RNA sequencing.
- Hierarchical clustering, recursive partitioning, and predictive modeling for immune markers.
Main Results:
- High TCR clonality with low T-cell fraction predicted lower overall survival.
- CD14+ monocytes correlated inversely with recurrence-free survival (RFS); CD4+ T-cell infiltration associated with higher RFS.
- Genes like PD-1, ICOS, BTLA, and CTLA4 were linked to longer RFS. CD4+ T-cells showed positive predictive value, while CD14+ monocytes and M2 macrophages had negative predictive values.
Conclusions:
- Immune cell infiltration, specifically CD4+ T-cells, CD14+ monocytes, and M2 macrophages, significantly predicts clinical outcomes in DDLPS.
- Future studies on checkpoint inhibitors in DDLPS should utilize immunosequencing and gene expression profiling for comprehensive immune landscape analysis.
