(P 141) TUMOUR-INFILTRATING IMMUNE CELLS IN SOFT TISSUE SARCOMA. IMPACT ON LOCAL RECURRENCE, DISTANT METASTASIS, AND OVERALL SURVIVAL.

Objective: Soft tissue sarcomas (STS) are known for their low immunogenic potential. Yet, due to their heterogeneity, differences in immune-profiles depending on histological subtypes and other clinico-pathological features can be expected. This retrospective study aimed at investigating the role of tumour-infiltrating immune cells on STS-patients’ outcome with regards to local recurrence (LR), distant metastasis (DM), and overall survival (OS).

Methods: Altogether, 188 patients (median age: 62.5 [IQR: 49.5-75] years; 46.3% females) with STS of the extremities, treated surgically for primarily localised disease at a single tertiary sarcoma centre, were retrospectively included. Median follow-up was 46.5 (IQR: 19-99) months. Tissue microarrays with 1266 cores in total were stained with multiplex immunohistochemistry. Analysis of the seven different cell types (CD20+ B-cells; CD68+ macrophages; CD3+, CD3+CD4+ helper, CD3+CD8+ cytotoxic, CD3+CD4+CD45RO+ helper memory, CD3+CD8+CD45RO+ cytotoxic memory T-cells) was performed with multispectral imaging. Phenotype abundance was correlated with clinico-pathological variables. Fine&Gray models for LR and DM (with death as competing event), and Cox-regression models for OS were calculated to investigate impact of prognostic variables. Findings upon immunohistochemistry were validated using gene expression data of TCGA-SARC specific for B- and T-cells, as well as macrophages.

Results: Patients aged > 62.5 years had lower B-cell (p=0.013) but higher macrophage abundance (p=0.002) than younger ones. Significant differences in immune cell abundance depending on histological subtypes were found, with generally higher levels in myxofibrosarcoma and undifferentiated pleomorphic sarcoma. In univariate analysis, high macrophage (p=0.003) and B-cell abundance (p=0.035) was associated with increased risk for LR. For high macrophage abundance (p=0.014), this significance prevailed in the multivariate analysis, irrespective of patient age, margin status, gender, or B-cell abundance. The remaining immune cells were not significantly associated with patient outcome.

Conclusion: Immune cell abundance in STS shows variations depending on clinico-pathological variables as age and histological subtype. High macrophage abundance appears as a negative prognostic factor for LR, irrespective of important clinical variables (e.g. margin status).