Nishimura Kenichi, Konishi Tatsuya, Ochi Toshiki, Watanabe Ryuta, Noda Terutaka, Fukumoto Tetsuya, Miura Noriyoshi, Miyauchi Yuki, Kikugawa Tadahiko, Takenaka Katsuto, Saika Takashi
Department of Urology, Ehime University Graduate School of Medicine, Toon 791-0295, Japan.
Department of Hematology, Clinical Immunology and Infectious Diseases, Ehime University Graduate School of Medicine, Toon 791-0295, Japan.
J Pers Med. 2022 May 28;12(6):888. doi: 10.3390/jpm12060888.
Immune checkpoint inhibitor (ICI) therapy increases the risk of immune-related adverse events (irAEs). In particular, combination checkpoint blockade (CCB) targeting inhibitory CTLA-4 and PD-1 receptors could lead to irAEs at a higher rate than ICI monotherapy. Management of irAEs is important while using ICIs. However, there are no reliable biomarkers for predicting irAEs. The aim of this study was to elucidate early B cell changes after CCB therapy in patients with renal cell carcinoma (RCC) and verify whether B cells can be a predictor of irAEs. This prospective cohort study was conducted with 23 Japanese patients with metastatic RCC. An increase in the proportion of CD21 B cells and CD21 memory B cells was confirmed following CCB therapy. Although there were no differences in clinical outcomes between irAE and no-irAE groups, the proportion of CD21 B cells at baseline was lower in the irAE group, with a significant increase after the first cycle of CCB therapy. Further analysis revealed a moderate correlation between irAEs and CD21 B cell levels at baseline (area under the curve: 0.83, cut-off: 3.13%, sensitivity: 92.3, specificity: 70.0). This finding indicates that patients with low baseline CD21 B cell levels warrant closer monitoring for irAEs. The clinical registration number by the Certified Review Board of Ehime University is No. 1902011.
免疫检查点抑制剂（ICI）疗法会增加免疫相关不良事件（irAE）的风险。特别是，针对抑制性CTLA-4和PD-1受体的联合检查点阻断（CCB）可能比ICI单药疗法导致更高发生率的irAE。在使用ICI时，irAE的管理很重要。然而，目前尚无可靠的生物标志物来预测irAE。本研究的目的是阐明肾细胞癌（RCC）患者接受CCB治疗后早期B细胞的变化，并验证B细胞是否可作为irAE的预测指标。本前瞻性队列研究纳入了23例日本转移性RCC患者。CCB治疗后证实CD21 B细胞和CD21记忆B细胞的比例增加。尽管irAE组和无irAE组的临床结局无差异，但irAE组基线时CD21 B细胞的比例较低，在CCB治疗的第一个周期后显著增加。进一步分析显示，irAE与基线时CD21 B细胞水平之间存在中度相关性（曲线下面积：0.83，临界值：3.13%，敏感性：92.3，特异性：70.0）。这一发现表明，基线CD21 B细胞水平较低的患者需要更密切地监测irAE。爱媛大学认证审查委员会的临床注册号为No. 1902011。
