(P 242) IMMUNE PROFILING OF UNDIFFERENTIATED PLEOMORPHIC SARCOMAS REVEALS DISTINCT PROGNOSTIC SUBGROUPS

Objective: UPS is a clinically aggressive and heterogeneous subtype of soft tissue sarcoma. The tumor microenvironment (TME) plays a critical role in UPS biology and likely influences prognosis and therapeutic response. However, detailed characterization of immune infiltration patterns and their clinical significance in UPS remains limited.

Methods: To investigate the immune landscape of UPS, we analyzed the TME of 74 primary UPS by H+E assessment for the presence of lymphoid aggregates (LA), immunohistochemistry (IHC) and RNA-sequencing (RNA-seq). IHC was performed for CD3, CD8, CD20, CD163, PD1, ICOS, OX40, and IDO1, and used to classify tumors into 3 distinct immune clusters: Immune High, Immune Intermediate, and Immune Low. MCP-counter was used to perform immune deconvolution using RNA-seq data to quantify the relative abundance of immune and stromal cell populations. We then evaluated the association between immune cluster defined by IHC, presence of LA, TME composition inferred by immune deconvolution, and patient survival. Kaplan-Meier survival analysis was used to assess the prognostic significance of the immune clusters.

Results: Distinct immune cell signatures were observed across the three immune clusters. The Immune High group showed greater infiltration of T cells, NK cells, cytotoxic markers, B cells, macrophages, and myeloid dendritic cells while the Immune Intermediate cluster demonstrated moderate levels of diverse immune populations and the Immune Low group exhibited sparse immune cell infiltration. These clusters also showed distinct patterns of LA, with LAs observed more frequently in Immune High tumors. Survival analysis revealed a significant difference in overall survival across immune clusters (log-rank p = 0.0062), with patients in the Immune High group exhibiting the most favorable outcomes and those in the Immune Low group having the worst prognosis.

Conclusion: Our findings highlight the prognostic importance of the TME in UPS. Integrated immune profiling using MCP-counter and IHC-based clustering reveals biologically distinct UPS subgroups associated with LA and clinical outcomes, supporting their potential role in guiding patient stratification and therapeutic strategies.