Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
J Exp Clin Cancer Res. 2024 May 31;43(1):155. doi: 10.1186/s13046-024-03074-z.
Longitudinal sampling of tumor tissue from patients with solid cancers, aside from melanoma and a few other cases, is often unfeasible, and thus may not capture the plasticity of interactions between the tumor and immune system under selective pressure of a given therapy. Peripheral blood analyses provide salient information about the human peripheral immunome while offering technical and practical advantages over traditional tumor biopsies, and should be utilized where possible alongside interrogation of the tumor. Some common blood-based biomarkers used to study the immune response include immune cell subsets, circulating tumor DNA, and protein analytes such as cytokines. With the recent explosion of immune checkpoint inhibitors (ICI) as a modality of treatment in multiple cancer types, soluble immune checkpoints have become a relevant area of investigation for peripheral immune-based biomarkers. However, the exact functions of soluble immune checkpoints and their roles in cancer for the most part remain unclear. This review discusses current literature on the production, function, and expression of nine soluble immune checkpoints - sPD-L1, sPD-1, sCTLA4, sCD80, sTIM3, sLAG3, sB7-H3, sBTLA, and sHVEM - in patients with solid tumors, and explores their role as biomarkers of response to ICI as well as to conventional therapies (chemotherapy, radiotherapy, targeted therapy, and surgery) in cancer patients.
对实体瘤患者的肿瘤组织进行纵向采样（黑色素瘤和其他少数情况除外）通常是不可行的，因此可能无法捕捉到在特定治疗的选择性压力下肿瘤与免疫系统之间相互作用的可塑性。外周血分析提供了有关人类外周免疫组的重要信息，同时相对于传统的肿瘤活检具有技术和实际优势，应尽可能与肿瘤的检测一起使用。一些用于研究免疫反应的常见基于血液的生物标志物包括免疫细胞亚群、循环肿瘤 DNA 和细胞因子等蛋白质分析物。随着免疫检查点抑制剂（ICI）作为多种癌症类型的治疗方式的迅速发展，可溶性免疫检查点已成为外周免疫为基础的生物标志物相关研究领域。然而，可溶性免疫检查点的确切功能及其在癌症中的作用在很大程度上仍不清楚。本文综述了目前关于 9 种可溶性免疫检查点（sPD-L1、sPD-1、sCTLA4、sCD80、sTIM3、sLAG3、sB7-H3、sBTLA 和 sHVEM）在实体瘤患者中的产生、功能和表达的文献，并探讨了它们作为对 ICI 以及对癌症患者的常规治疗（化疗、放疗、靶向治疗和手术）反应的生物标志物的作用。
