Prognostic Value of Fas/Fas Ligand Expression on Circulating Tumor Cells (CTCs) and Immune Cells in the Peripheral Blood of Patients with Metastatic Breast Cancer.

Simple Summary: The Fas/Fas ligand (FasL) system is an apoptosis-regulating pathway that holds a key role in tumor immune surveillance and metastasis. Although this pathway has been extensively investigated in pre-clinical models and in primary tumor tissues, however its role in the periphery is largely unexplored. To this end, the expression of Fas/FasL was for the first time assessed on circulating tumor cells (CTCs) and matched peripheral blood mononuclear cells (PBMCs) in the peripheral blood of patients with metastatic breast cancer (BC). The results show that Fas and FasL are frequently expressed on BC patients' CTCs, with Fas/FasL-co-expressing CTCs emerging as a poor prognostic marker predicting a high risk for disease progression. On the other hand, Fas and FasL were also frequently expressed on BC patients' PBMCs, and Fas/FasL co-expression on PBMCs emerged as a favorable prognostic marker associated with a low risk for death. These results show that the assessment of Fas/FasL expression on CTCs and PBMCs can provide valuable prognostic information for patients with metastatic BC, and highlight their potential role in the peripheral immune response and metastatic progression of BC. The Fas/Fas ligand (FasL) system is a major apoptosis-regulating pathway with a key role in tumor immune surveillance and metastasis. The expression of Fas/FasL on mammary tumor tissues holds prognostic value for breast cancer (BC) patients. We herein assessed Fas/FasL expression on circulating tumor cells (CTCs) and matched peripheral blood mononuclear cells (PBMCs) from 98 patients with metastatic BC receiving first-line treatment. Fas+, FasL+, and Fas+/FasL+ CTCs were identified in 88.5%, 92.3%, and 84.6% of CTC-positive patients, respectively. In addition, Fas+/FasL+, Fas-/FasL+, and Fas-/FasL- PBMCs were identified in 70.3%, 24.2%, and 5.5% of patients, respectively. A reduced progression-free survival (PFS) was revealed among CTC-positive patients (median PFS: 9.5 versus 13.4 months; p = 0.004), and specifically among those harboring Fas+/FasL+ CTCs (median PFS: 9.5 vs. 13.4 months; p = 0.009). On the other hand, an increased overall survival (OS) was demonstrated among patients with Fas+/FasL+ PBMCs rather than those with Fas-/FasL+ and Fas-/FasL- PBMCs (median OS: 35.7 vs. 25.9 vs. 14.4 months, respectively; p = 0.008). These data provide for the first time evidence on Fas/FasL expression on CTCs and PBMCs with significant prognostic value for patients with metastatic BC, thus highlighting the role of the Fas/FasL system in the peripheral immune response and metastatic progression of BC. [ABSTRACT FROM AUTHOR]