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.
Fas/Fas配体(FasL)系统是调控细胞凋亡的主要通路,在肿瘤免疫监视和转移过程中发挥关键作用。乳腺肿瘤组织中Fas/FasL的表达对乳腺癌(BC)患者具有预后评估价值。本研究对98例接受一线治疗的转移性BC患者循环肿瘤细胞(CTCs)及匹配的外周血单个核细胞(PBMCs)的Fas/FasL表达进行检测。结果显示:在CTC阳性患者中,分别有88.5%、92.3%和84.6%的患者检出Fas+、FasL+及Fas+/FasL+ CTCs;同时,70.3%、24.2%和5.5%的患者分别检出Fas+/FasL+、Fas-/FasL+及Fas-/FasL- PBMCs。生存分析表明:CTC阳性患者无进展生存期(PFS)显著缩短(中位PFS:9.5个月 vs 13.4个月;p=0.004),其中携带Fas+/FasL+ CTCs的患者PFS缩短尤为显著(中位PFS:9.5个月 vs 13.4个月;p=0.009)。另一方面,与携带Fas-/FasL+及Fas-/FasL- PBMCs的患者相比,携带Fas+/FasL+ PBMCs的患者总生存期(OS)显著延长(中位OS分别为:35.7个月 vs 25.9个月 vs 14.4个月;p=0.008)。本研究首次证实CTCs和PBMCs的Fas/FasL表达对转移性BC患者具有重要预后价值,从而揭示了Fas/FasL系统在BC外周免疫应答及转移进展中的作用。