Immune-cell Infiltration in High-grade Soft Tissue Sarcomas; Prognostic Implications of Tumor-associated Macrophages and B-cells

Background: Soft tissue sarcomas are rare, morphologically, and genetically heterogenous. Though the tumors display abundant tumor stroma with infiltrating immune cells, the prognostic impact of various immunologic markers in sarcoma remains poorly defined. We aimed to characterize the immune landscape of a treatment-naïve cohort of soft tissue sarcoma of the extremities and the trunk wall with correlations to metastasis-free survival.

Materials And Methods: We surveyed immunohistochemical expression patterns for CD163, CD20, CD3, CD8, and FOXP3 in 134 adult high-grade leiomyosarcomas, liposarcomas, and synovial sarcomas.

Results: Macrophages outnumbered tumor-infiltrating lymphocytes. High CD163 infiltration was identified in 49% of the tumors and was overrepresented (66%) in leiomyosarcoma compared to liposarcoma (46%) and synovial sarcoma (9%). Tumor-grade also correlated with CD163 positivity with high expression in 53% of the high-grade lesions and 28% in low-grade tumors. Infiltrating CD3, CD8 and FOXP3-positive T-cells were significantly more prevalent in leiomyosarcomas than in liposarcomas/synovial sarcomas. CD20 B-cells were identified only in 14% of the STS. Correlation to established prognostic factors revealed a correlation between CD163 macrophages and necrosis and predicted an increased risk of metastases. No correlation between CD20 B-cells and known prognostic factors could be established, though CD20 B-cells infiltration predicted improved overall survival.

Conclusion: We confirm that tumor-infiltrating macrophages outnumber tumor-infiltrating lymphocytes in soft tissue sarcoma and signify an increased risk of metastasis. CD20 B-cells are scarce in STS and correlate to improved survival. To date, immunotherapeutic strategies directed against T-cells have shown limited effect in soft tissue sarcoma. Our observations suggest that immunomodulatory agents focusing on macrophages may be worthwhile for further investigations in this tumor type. Further studies exploring the prognostic and predictive significance of CD20 B cells are warranted.