Department of Urology, Qilu Hospital, Shandong University, 107 Wenhua West Road, Jinan 250012, PR China.
Department of Medical Oncology, Qilu Hospital, Shandong University, 107 Wenhua West Road, Jinan 250012, PR China.
Int J Med Sci. 2021 Jan 1;18(1):99-108. doi: 10.7150/ijms.47384. eCollection 2021.
T-helper (Th) 22 cells serve an essential role in different types of tumors and autoimmune diseases. No research has been conducted to study the role of Th22 cells in the pathogenesis of renal cell carcinoma (RCC). We aimed to evaluate the prognostic value of circulating Th22, Th17, and Th1 cells in RCC patients. Thirty-two newly diagnosed RCC patients and thirty healthy controls were enlisted in the research. Their peripheral blood was collected, and the frequencies of circulating Th22, Th17, and Th1 cells were detected by flow cytometry. Plasma IL-22 concentrations were examined by an enzyme-linked immunosorbent assay (ELISA). Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to identify the mRNA expression levels of aromatic hydrocarbon receptor (AHR) and RAR-associated orphan receptor C (RORC) in peripheral blood mononuclear cells (PBMC). Compared with the healthy control group, the frequency of circulating Th22 and Th17 cells and concentrations of plasma IL-22 were significantly increased in RCC patients. However, there was no significant difference in the frequency of Th1 cells. A positive correlation between Th22 cells and plasma IL-22 levels was found in RCC patients. Also, there was a significant positive correlation between Th22 and Th17 cells in RCC patients. An up-regulated expression of AHR and RORC transcription factors were also observed in RCC patients. As tumor stage and grade progressed, the frequencies of Th22 and Th17 cells and the level of plasma IL-22 significantly increased. Meanwhile, there was a positive correlation between Th22 and Th17 cells and RCC tumor stage or grade. Furthermore, patients with high Th22 or Th17 cells frequency displayed a decreased trend in survival rate. Our research indicated that the increased circulating Th22 and Th17 cells and plasma IL-22 may be involved in the pathogenesis of RCC and may be involved in the occurrence and development of tumors. Th22 cells, plasma IL-22, and Th17 cells may be promising new clinical biomarkers and may be used as cellular targets for RCC therapeutic intervention.
辅助性 T 细胞(Th)22 细胞在不同类型的肿瘤和自身免疫性疾病中起着至关重要的作用。目前尚未有研究探讨 Th22 细胞在肾细胞癌(RCC)发病机制中的作用。我们旨在评估循环 Th22、Th17 和 Th1 细胞在 RCC 患者中的预后价值。研究纳入了 32 名新诊断的 RCC 患者和 30 名健康对照者。采集他们的外周血,通过流式细胞术检测循环 Th22、Th17 和 Th1 细胞的频率。通过酶联免疫吸附试验(ELISA)检测血浆 IL-22 浓度。使用定量逆转录-聚合酶链反应(RT-PCR)检测外周血单个核细胞(PBMC)中芳香烃受体(AHR)和维甲酸相关孤儿受体 C(RORC)的 mRNA 表达水平。与健康对照组相比,RCC 患者循环 Th22 和 Th17 细胞的频率以及血浆 IL-22 浓度显著升高,而 Th1 细胞的频率无显著差异。RCC 患者中 Th22 细胞与血浆 IL-22 水平呈正相关。此外,RCC 患者中 Th22 和 Th17 细胞之间也存在显著的正相关。RCC 患者中 AHR 和 RORC 转录因子的表达也上调。随着肿瘤分期和分级的进展,Th22 和 Th17 细胞的频率以及血浆 IL-22 水平显著升高。同时,Th22 与 Th17 细胞与 RCC 肿瘤分期或分级呈正相关。此外,Th22 或 Th17 细胞频率高的患者生存率呈下降趋势。我们的研究表明,循环 Th22 和 Th17 细胞及血浆 IL-22 的增加可能参与了 RCC 的发病机制,可能参与了肿瘤的发生和发展。Th22 细胞、血浆 IL-22 和 Th17 细胞可能是有前途的新的临床生物标志物,并可作为 RCC 治疗干预的细胞靶点。