Work

Single-cell analysis reveals the potential immunoregulatory role of C3 + malignant cell subpopulations in dedifferentiated liposarcoma

Year: 2026

Type: article

Abstract: BACKGROUND: Dedifferentiated liposarcoma (DDLPS), a rare disease with limited research, exhibits resistance to radiotherapy and chemotherapy. Few reports have analyzed the tumor microenvironment of retroperitoneal undifferentiated liposarcoma using single-cell sequencing. METHODS: Single-cell analysis of three retroperitoneal DDLPS cases characterized the cellular and immune microenvironment. RESULTS: Our findings reveal significant heterogeneity among malignant cells in DDLPS, with chromosome 6 deletions being prevalent across malignant cell subpopulations and potentially linked to reduced immunogenicity based on pathway analyses. Notably, the coexistence of CD8 + T cell exhaustion and cytotoxicity reflects a continuum of exhaustion transition. Moreover, we identify a C3 + malignant cell subpopulation with ECM remodeling, angiogenesis, and activated complement pathway. Further exploration suggested that C3 + malignant cells may recruit IL2RA+ regulatory T cells and SPP1 + macrophages through the C3-C3aR1 axis. CONCLUSION: Our findings provide new insights into the application of immunotherapy in sarcoma.

Source: BMC Cancer

DOI: 10.1186/s12885-026-16750-4