Department of Hematology and Bone Marrow Transplantation, Saint Savvas Regional Cancer Hospital , Athens , Greece.
Department of Immunology and Histocompatibility, "Evangelismos" General Hospital , Athens , Greece.
Leuk Lymphoma. 2019 Oct;60(10):2457-2463. doi: 10.1080/10428194.2019.1581935. Epub 2019 Apr 5.
The aim of the present study was to identify biomarkers predictive of the outcome of patients with high-risk myelodysplastic syndrome and oligoblastic acute myeloid leukemia (AML) treated with 5-azacytidine (AZA). We prospectively examined the association between NK-cytotoxic activity, myeloid-derived suppressor cells (MDSCs), and T-regulatory cells (Tregs) on the overall survival (OS) of patients. Patients with NK-cytotoxicity above a critical threshold had a longer duration of response and survived longer than patients with severe impairment of NK-cytotoxicity. The numbers of MDSCs, and Tregs in the PB of patients after a short exposure to AZA were not different from normal donors. In conclusion, the results of our study suggest that the therapeutic activity of AZA is at least partly mediated by an immunomodulatory effect. To our knowledge, this is the first study reported so far, that shows a positive correlation between NK cytotoxicity and OS of AZA-treated patients.
本研究旨在确定预测接受 5-氮杂胞苷（AZA）治疗的高危骨髓增生异常综合征和少突性急性髓系白血病（AML）患者预后的生物标志物。我们前瞻性地研究了 NK 细胞毒性、髓系来源的抑制细胞（MDSCs）和 T 调节细胞（Tregs）与患者总生存期（OS）之间的关联。NK 细胞毒性超过临界阈值的患者具有更长的缓解期和更长的生存期，而 NK 细胞毒性严重受损的患者则较短。AZA 短期暴露后患者 PB 中的 MDSCs 和 Tregs 与正常供体无差异。总之，我们的研究结果表明，AZA 的治疗活性至少部分是通过免疫调节作用介导的。据我们所知，这是迄今为止首次报道的研究，表明 NK 细胞毒性与 AZA 治疗患者的 OS 之间存在正相关。
