Vallacchi V, Bergamaschi L, F. Perrone, F. Rini, L. Rivoltini, C. Castelli, A. Gronchi, C. Colombo
Annals of Onc
Background: Desmoid fibromatosis (DF) is a locally aggressive rare tumor with high recurrence rate after surgery and unpredictable clinical course. Standard of care for DF patients is active surveillance; 30% of cases undergo disease progression and shift to treatment. Biomarkers discriminating aggressive DF and predicting progressive disease are needed. DF harbors mutations in ?-catenin and a transcriptional Â‘inflammatory phenotypeÂ’ (PMID: 28627792). Cancer-associated inflammation is fostered by systemic factors and detectable in circulating immune cells. Blood leukocytes thus represent a promising source of prognostic biomarkers for DF patients. In this study we investigate phenotypic and functional features of peripheral blood immune cells to identify DF patients at risk of progression and guide tailored therapeutic approaches. Methods: This is a prospective observational study enrolling DF patients (n=80). Tumor and blood samples collected at diagnosis and during active surveillance will be studied by 1. transcriptomic analysis of DF biopsies; 2. multiparametric flowcytometry and functional profiling of blood cells; 3. RNA profiling of whole blood 4. evaluation of plasma levels of cyto/chemokine and ctDNA of ?-catenin variants. Levels of blood analytes will be correlated with patientsÂ’ clinical outcome and integrated with immunological parameters. Results: Peripheral blood immune profile of 40 cases shows that patients display at baseline an altered myeloid profile with respect to healthy donors. An increase in activated granulocytes and granulocytic myeloid-derived suppressor cells, detected by differential co-expression of CD15, CD11b, CD16 and LOX1, is observed, concomitantly, with a boost of monocyte subsets, defined by co-expression of CD33, CD11b, CD14, CD16, HLA-DR and PDL1. These changes are maintained during follow-up in a specific subset of patients. Conclusions: Systemic alterations of immunosuppressive and inflammatory myeloid cell subsets feature the peripheral blood of DF patients and may represent a marker of disease aggressiveness. Transcriptomic data of DF biopsies and of plasma analytes will be also presented.