Papadaki Maria A, Papadaki Eleni, Chatziavraam Sofia, Aggouraki Despoina, Michaelidou Kleita, Fotsitzoudis Charalampos, Vassilakopoulou Maria, Mavroudis Dimitrios, Agelaki Sofia
Laboratory of Translational Oncology, Medical School, University of Crete, Heraklion, 70013 Crete, Greece.
Department of Medical Oncology, University General Hospital of Heraklion, 71500 Heraklion, Greece.
Cancers (Basel). 2024 Aug 23;16(17):2927. doi: 10.3390/cancers16172927.
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; = 0.004), and specifically among those harboring Fas+/FasL+ CTCs (median PFS: 9.5 vs. 13.4 months; = 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; = 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）系统是主要的凋亡调节途径，在肿瘤免疫监视和转移中起关键作用。Fas/FasL在乳腺肿瘤组织上的表达对乳腺癌（BC）患者具有预后价值。我们在此评估了98例接受一线治疗的转移性BC患者循环肿瘤细胞（CTC）及配对的外周血单核细胞（PBMC）上Fas/FasL的表达。分别在88.5%、92.3%和84.6%的CTC阳性患者中鉴定出Fas+、FasL+和Fas+/FasL+ CTC。此外，分别在70.3%、24.2%和5.5%的患者中鉴定出Fas+/FasL+、Fas-/FasL+和Fas-/FasL- PBMC。CTC阳性患者的无进展生存期（PFS）缩短（中位PFS：9.5个月对13.4个月；P = 0.004），特别是那些携带Fas+/FasL+ CTC的患者（中位PFS：9.5个月对13.4个月；P = 0.009）。另一方面，Fas+/FasL+ PBMC患者的总生存期（OS）延长而非Fas-/FasL+和Fas-/FasL- PBMC患者（中位OS：分别为35.7个月对25.9个月对14.4个月；P = 0.008）。这些数据首次提供了关于CTC和PBMC上Fas/FasL表达对转移性BC患者具有显著预后价值的证据，从而突出了Fas/FasL系统在BC外周免疫反应和转移进展中的作用。
