Abstract 5613: Tumor glucose metabolism profiles detected via [18F]-FDG PET/CT correlate with the immune landascape in soft-tissue sarcomas

Abstract Background: Improving the assessment of the immune landscape of soft-tissue sarcoma (STS) through imaging biomarkers could help better selecting and monitoring patients that could benefit from immunotherapy. Our aim was identify whether metabolic patterns of soft-tissue sarcoma (STS) on pre-treatment 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET/CT) were associated with different immune profiles on molecular and cellular levels. Methods: This single-center prospective study included consecutive adult patients with newly-diagnosed, non-metastatic, high-grade STS treated in a curative intent with available pre-treatement 18F-FDG-PET/CT. Maximal standardized uptake value (SUVmax), SUVpeak, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were extracted. A cross-validated principal component analysis (PCA) was developed on the PET/CT metrics. The first two principal components (PC1 and PC2) and an unsupervised metabolic classifications were computed. Differential gene expression (DGE), oncogenesis pathways analyses, complexity index in sarcoma (CINSARC) molecular signature and immunohistochemistry panels (CD8, CD14, CD20, CD45, CD68, c-MAF) were performed. Correlations between nuclear imaging, immunohistochemistry and transcriptomics data were achieved. Results: 85 patients were included (median age: 62 years, 37 women) between 2016 and 2021. The robust PCA defined 3 metabolic groups (high [n=21], intermediate [n=15] and low [n=49]). PC1 reflected the tumor metabolism and PC2 the size and amount of necrosis. Transcriptomics and immunohistochemistry data were available in 32 and 31 patients, respectively. PC1 was significantly positively correlated with CINSARC (P=0.0029) and the cellular densities in CD8+, CD14+, CD45+, CD68+ and c-MAF (range of P-values: 0.0175-0.0499). The metabolic-high group was characterized by the upregulation of 13 immune pathways, including ICOS, CD27, IFNG, CXCL9-10/CXCL3 genes. Conclusion: Metabolic profiles on 18F-FDG-PET/CT of high-grade STS highlights distinct immune profiles, which could pave the way for potential biomarkers of STS immunophenotyping. Citation Format: Amandine Crombe, Frédéric Bertolo, Jean-Philippe Guegan, Alban Bessede, Raul Perret, Mariella Spalato-Ceruso, Maud Toulmonde, Audrey Laroche, Francois Le Loarer, Vanessa Chaire, Michèle Kind, Carlo Lucchesi, Antoine Italiano. Tumor glucose metabolism profiles detected via [18F]-FDG PET/CT correlate with the immune landascape in soft-tissue sarcomas. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5613.