作为肾细胞癌免疫相关不良事件预测指标的T细胞受体库
T-Cell Receptor Repertoire as a Predictor of Immune-Related Adverse Events in Renal Cell Carcinoma.
作者信息
Kobayashi Takuro, Nagata Masayoshi, Ikehata Yoshihiro, Nagashima Yuki, Nagaya Naoya, Lu Yan, Horie Shigeo
机构信息
Department of Urology, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan.
Department of Urology, Shizuoka Hospital, Juntendo University, Shizuoka 410-2211, Japan.
出版信息
Curr Issues Mol Biol. 2023 Nov 9;45(11):8939-8949. doi: 10.3390/cimb45110561.
Immune checkpoint inhibitors (ICIs) are effective in treating renal cell carcinoma (RCC) but can also cause immune-related adverse events (irAEs). The relationship between irAEs and the T-cell receptor (TCR) repertoire in RCC patients treated with ICIs remains unclear. We analyzed the relationship between the severity and diversity of irAEs and the TCR repertoire in RCC patients who received dual checkpoint inhibitors (ipilimumab + nivolumab). The TCRβ (TRB) repertoires were characterized in peripheral blood samples from six patients with RCC before the initiation of ICI therapy. The diversity and clonality of the TCR repertoire were compared between patients with grade 2 and grade 3 irAEs. The median proportion of top 10 unique reads in the TCR repertoire was significantly higher in grade 3 compared with grade 2 irAEs in RCC patients receiving immune checkpoint inhibitors (grade 2: 0.196%; grade 3: 0.346%; = 0.0038). We provide insight into the relationship between TCR repertoire and irAEs in RCC patients treated with ICIs. TCR repertoire clonality may be associated with the development of irAEs in RCC patients.
免疫检查点抑制剂（ICIs）在治疗肾细胞癌（RCC）方面有效，但也会引发免疫相关不良事件（irAEs）。接受ICIs治疗的RCC患者中，irAEs与T细胞受体（TCR）库之间的关系仍不明确。我们分析了接受双重检查点抑制剂（伊匹木单抗+纳武单抗）治疗的RCC患者中irAEs的严重程度和多样性与TCR库之间的关系。对6例RCC患者在ICI治疗开始前外周血样本中的TCRβ（TRB）库进行了特征分析。比较了2级和3级irAEs患者TCR库的多样性和克隆性。在接受免疫检查点抑制剂治疗的RCC患者中，3级患者TCR库中前10个独特读数的中位数比例显著高于2级患者（2级：0.196%；3级：0.346%；P=0.0038）。我们深入了解了接受ICIs治疗的RCC患者中TCR库与irAEs之间的关系。TCR库的克隆性可能与RCC患者irAEs的发生有关。
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