Cancer Vaccine Development Division, Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan.
Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Japan.
J Immunol Res. 2017;2017:1423683. doi: 10.1155/2017/1423683. Epub 2017 Apr 27.
High-mobility group box 1 (HMGB1) is a nuclear protein that is known to be secreted into extracellular fluids from injured cells, activated macrophages, and tumor cells. The clinical correlation of circulating HMGB1 levels with various diseases including cancer has been reported. However, there is no information on HMGB1 levels in cancer patients treated with peptide vaccination. In the present study, we investigated the plasma levels of HMGB1 during personalized peptide vaccination in patients with recurrent ovarian cancer. Frozen plasma samples of 39 patients from previously conducted clinical trials were used in this study. HMGB1 levels were decreased after the 1st cycle of vaccination from their prevaccination levels. However, no correlation was observed between HMGB1 and overall survival (OS). The correlation between plasma HMGB1 levels and other biomarker levels was further analyzed by scatter plot, revealing that HMGB1 levels after the 1st cycle of vaccination were significantly correlated with myeloid-derived suppressor cell (MDSC) frequency after the 1st cycle of vaccination ( = 0.357, = 0.032). Chi-square test showed that epitope spreading was significantly related with changes of HMGB1 ( = 0.030). These results suggest that plasma HMGB1 is a possible biomarker for cancer vaccine therapy, although direct correlation with OS has not been obtained. This trial is registered with Clinical Trial Registry under trial numbers UMIN000003083 and UMIN000001482.
高迁移率族蛋白 B1（HMGB1）是一种核蛋白，已知其可从受损细胞、活化的巨噬细胞和肿瘤细胞分泌到细胞外液中。已经报道了循环 HMGB1 水平与包括癌症在内的各种疾病的临床相关性。然而，关于接受肽疫苗接种的癌症患者的 HMGB1 水平尚无信息。在本研究中，我们研究了复发性卵巢癌患者接受个体化肽疫苗接种期间血浆 HMGB1 水平。本研究使用了之前进行的临床试验中 39 名患者的冷冻血浆样本。在接种第 1 周期后，HMGB1 水平从接种前水平降低。但是，HMGB1 与总生存期（OS）之间未观察到相关性。通过散点图进一步分析了血浆 HMGB1 水平与其他生物标志物水平之间的相关性，结果表明接种第 1 周期后的 HMGB1 水平与接种第 1 周期后的髓样来源抑制细胞（MDSC）频率呈显著相关（ = 0.357， = 0.032）。卡方检验表明表位扩展与 HMGB1 的变化显著相关（ = 0.030）。这些结果表明，血浆 HMGB1 可能是癌症疫苗治疗的生物标志物，尽管尚未获得与 OS 的直接相关性。该试验在临床试验注册处注册，注册号为 UMIN000003083 和 UMIN000001482。
