Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
Br J Haematol. 2021 Mar;192(6):951-967. doi: 10.1111/bjh.16497. Epub 2020 Feb 10.
Immunotherapies have emerged as highly promising approaches to treat cancer patients. Allogeneic haematopoietic cell transplantation (HCT) is the most validated tumour immunotherapy available to date but its clinical efficacy is limited by toxicities, such as graft-versus-host disease (GVHD) and treatment resistance leading to relapse. The problems with new cellular therapies and checkpoint inhibitors are similar. However, development of biomarkers post-HCT, particularly for toxicities, has taken off in the last decade and has expanded greatly. Thanks to the advances in genomics, transcriptomics, proteomics and cytomics technologies, blood biomarkers have been identified and validated in promising diagnostic tests, prognostic tests stratifying for future occurrence of GVHD, and predictive tests for responsiveness to GVHD therapy and non-relapse mortality. These biomarkers may facilitate timely and selective therapeutic intervention. This review outlines a path from biomarker discovery to first clinical correlation, focusing on soluble STimulation-2 (sST2) - the interleukin (IL)-33-decoy receptor - which is the most validated biomarker.
免疫疗法已成为治疗癌症患者的极具前景的方法。同种异体造血细胞移植（HCT）是迄今为止最有效的肿瘤免疫疗法，但由于移植物抗宿主病（GVHD）和治疗耐药导致复发等毒性，其临床疗效受到限制。新型细胞疗法和检查点抑制剂存在的问题相似。然而，HCT 后生物标志物的开发，特别是针对毒性的开发，在过去十年中取得了飞速发展。得益于基因组学、转录组学、蛋白质组学和细胞组学技术的进步，血液生物标志物已在有前途的诊断测试、预测 GVHD 未来发生的预后测试以及预测 GVHD 治疗反应和非复发死亡率的预测测试中得到了鉴定和验证。这些生物标志物可能有助于及时进行有针对性的治疗干预。本综述概述了从生物标志物发现到首次临床相关性的途径，重点介绍了白细胞介素（IL）-33 诱饵受体可溶性 STimulation-2（sST2），这是最有效的验证生物标志物。
