Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
J Immunol. 2013 Jun 15;190(12):6250-8. doi: 10.4049/jimmunol.1300022. Epub 2013 May 15.
The interaction between CD27 and its ligand, CD70, has been implicated in regulating cellular immune responses to cancer. In this article, we report on the role of soluble CD27 (sCD27) in T cell activation and its elevation in the serum of cancer patients after immunotherapy. In vitro, sCD27 is preferentially derived from activated CD4(+) T cells. Adding sCD27 to stimulated PBMCs increases T cell activation and proliferation, and is associated with the immunologic synapse-related proteins myosin IIA, high mobility group box 1, and the TCR Vβ-chain. The pool of serum sCD27 is shown to be greater in healthy donors than in cancer patients. However, metastatic cancer patients treated with immunotherapy showed a significant increase in the serum sCD27-pool posttherapy (p < 0.0005); there was also an increased trend toward an association between enhanced sCD27-pool posttherapy and overall survival (p = 0.022). The identification of sCD27 as an immune modulator associated with enhanced human T cell activation in vitro and in vivo provides a rationale for developing new immunotherapeutic strategies aimed at enhancing sCD27 for treating cancer and potentially other diseases.
CD27 与其配体 CD70 的相互作用被认为在调节针对癌症的细胞免疫反应中发挥了作用。在本文中，我们报告了可溶性 CD27（sCD27）在 T 细胞激活中的作用及其在免疫治疗后癌症患者血清中的升高。在体外，sCD27 主要来源于活化的 CD4(+)T 细胞。向刺激的 PBMC 中添加 sCD27 可增加 T 细胞的激活和增殖，并与免疫突触相关蛋白肌球蛋白 IIA、高迁移率族蛋白 1 和 TCR Vβ 链相关。与健康供体相比，血清 sCD27 库在癌症患者中更大。然而，接受免疫治疗的转移性癌症患者在治疗后血清 sCD27 库显著增加（p < 0.0005）；治疗后增强的 sCD27 库与总生存期之间也存在增强的趋势（p = 0.022）。sCD27 作为一种与体外和体内增强人类 T 细胞激活相关的免疫调节剂的鉴定，为开发旨在增强 sCD27 以治疗癌症和潜在其他疾病的新免疫治疗策略提供了依据。
