Department of Melanoma Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Translational Molecular Pathology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Oncoimmunology. 2022 Sep 22;11(1):2124678. doi: 10.1080/2162402X.2022.2124678. eCollection 2022.
Acute kidney injury (AKI) occurs in ~20% of patients receiving immune checkpoint inhibitor (ICI) therapy; however, only 2-5% will develop ICI-mediated immune nephritis. Conventional tests are nonspecific in diagnosing disease pathology and invasive procedures (i.e. kidney biopsy) may not be feasible. In other autoimmune renal diseases, urinary immune cells correlated with the pathology or were predictive of disease activity. Corresponding evidence and analysis are absent for ICI-mediated immune nephritis. We report the first investigation analyzing immune cell profiles of matched kidney biopsies and urine of patients with ICI-AKI. We demonstrated the presence of urinary T cells in patients with immune nephritis by flow cytometry analysis. Clonotype analysis of T cell receptor (TCR) sequences confirmed enrichment of kidney TCRs in urine. As ICI therapies become standard of care for more cancers, noninvasively assessing urinary immune cells of ICI therapy recipients can facilitate clinical management and an opportunity to tailor ICI-nephritis treatment.
急性肾损伤(AKI)发生在接受免疫检查点抑制剂(ICI)治疗的患者中约 20%;然而,只有 2-5%会发展为 ICI 介导的免疫性肾炎。常规检测在诊断疾病病理方面缺乏特异性,且侵入性操作(即肾活检)可能不可行。在其他自身免疫性肾脏疾病中,尿液中的免疫细胞与病理相关,或可预测疾病活动。而对于 ICI 介导的免疫性肾炎,尚无相应的证据和分析。我们首次报道了分析 ICI-AKI 患者匹配的肾活检和尿液中免疫细胞特征的研究。通过流式细胞术分析,我们证明了免疫性肾炎患者尿液中存在 T 细胞。T 细胞受体(TCR)序列的克隆型分析证实了尿液中肾脏 TCR 的富集。随着 ICI 治疗成为更多癌症的标准治疗方法,非侵入性地评估 ICI 治疗接受者的尿液免疫细胞可以促进临床管理,并为 ICI-肾炎的治疗提供机会。