Department of Pediatrics, Department of Microbiology Immunology, and Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, 46202 Indianapolis, IN.
Mosaiques-Diagnostics GmbH, 30659 Hannover, Germany.
Proteomics Clin Appl. 2019 Mar;13(2):e1800145. doi: 10.1002/prca.201800145. Epub 2018 Oct 17.
Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective form of tumor immunotherapy available to date. However, while HSCT can induce beneficial graft-versus-leukemia (GVL) effect, the adverse effect of graft-versus-host disease (GVHD), which is closely linked to GVL, is the major source of morbidity and mortality following HSCT. Until recently, available diagnostic and staging tools frequently fail to identify those at higher risk of disease progression or death. Furthermore, there are shortcomings in the prediction of the need for therapeutic interventions or the response rates to different forms of therapy. The past decade has been characterized by an explosive evolution of proteomics technologies, largely due to important advances in high-throughput MS instruments and bioinformatics. Building on these opportunities, blood biomarkers have been identified and validated both as promising diagnostic tools, prognostic tools that risk-stratify patients before future occurrence of GVHD and as predictive tools for responsiveness to GVHD therapy and non-relapse mortality. These biomarkers might facilitate timely and selective therapeutic intervention. This review summarizes current information on clinical proteomics for GVHD as well as other complications following HSCT. Finally, it proposes future directions for the translation of clinical proteomics to discovery of new potential therapeutic targets to the development of drugs.
异基因造血干细胞移植（HSCT）是迄今为止最有效的肿瘤免疫治疗形式。然而，虽然 HSCT 可以诱导有益的移植物抗白血病（GVL）效应，但与 GVL 密切相关的移植物抗宿主病（GVHD）的不良反应是 HSCT 后发病率和死亡率的主要来源。直到最近，现有的诊断和分期工具经常无法识别那些疾病进展或死亡风险较高的患者。此外，在预测治疗干预的需求或对不同形式治疗的反应率方面也存在不足。过去十年的特点是蛋白质组学技术的爆炸式发展，这主要得益于高通量 MS 仪器和生物信息学的重要进展。利用这些机会，血液生物标志物已被确定和验证，作为有前途的诊断工具、在 GVHD 发生之前对患者进行风险分层的预后工具，以及预测 GVHD 治疗反应和非复发死亡率的工具。这些生物标志物可能有助于及时和有选择性的治疗干预。这篇综述总结了目前关于 HSCT 后 GVHD 及其他并发症的临床蛋白质组学信息。最后，它提出了将临床蛋白质组学转化为发现新的潜在治疗靶点和开发药物的未来方向。
