Tumor morphology and location associate with immune cell composition in pleomorphic sarcoma

Area of Science:

• Oncology
• Immunology
• Cancer Biology

Background:

• Soft-tissue sarcomas (STS) are rare mesenchymal malignancies, with undifferentiated pleomorphic sarcoma (UPS) being a common subtype.
• Current clinical stratification of UPS relies on outdated tumor metrics like size and depth, with limited understanding of the tumor microenvironment's role.
• The tumor microenvironment's impact on UPS progression and patient outcomes requires further investigation.

Purpose of the Study:

• To investigate the correlation between the tumor microenvironment's immune cell composition and clinicopathologic parameters in UPS.
• To explore the relationship between immune cell infiltration, tumor size, depth, and patient survival in UPS.

Main Methods:

• Single-cell flow cytometric immune profiling of 15 freshly resected UPS tumors.
• Integration of immune profiling data with clinical, histopathologic, and outcomes data from prospective and retrospective UPS patient cohorts.

Main Results:

• Identified correlations between UPS tumor physiology/anatomy and immune cell composition.
• Found an inverse correlation between tumor-infiltrating CD8+ T cells and UPS tumor size.
• Demonstrated a positive correlation between tumor-infiltrating CD8+ T cells and overall survival in UPS patients.
• Observed an association between tumor depth (deep vs. superficial) and the frequency of CD4+ PD1hi infiltrating T cells.

Conclusions:

• The study provides an immune-based analysis of the UPS tumor microenvironment.
• Tumor-infiltrating lymphocyte composition varies based on UPS tumor size and depth.
• These findings highlight the potential of immune profiling for understanding UPS biology and patient stratification.