Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Cell Mol Biol (Noisy-le-grand). 2024 Apr 28;70(4):15-22. doi: 10.14715/cmb/2024.70.4.3.
IL-21 is a cytokine with versatile antitumor and pro-tumorigenic activities. It is mainly produced by CD4+ T cells and B cells are one of its pivotal targets. In this study, we assessed and compared the expression of IL-21 by CD4+ T cells and the IL-21 receptor (IL-21R) on B cells in the peripheral blood of women with breast cancer and healthy individuals. Blood samples were taken from both patients and controls. Mononuclear cells were seperated using Ficoll-Hypaque density gradient centrifugation. These isolated cells were then stained with either anti-CD19/anti-IL-21R or anti-CD4/anti-IL-21 antibodies and analyzed using flow cytometry. The results showed that there was no significant difference in the percentage of IL-21R+ B cells and IL-21+CD4+ T cells between patients and controls. However, the percentage of CD4+ T cells decreased significantly in patients with breast cancer (P=0.003). This decline was observed from the early stage and before lymph node (LN) involvement. In comparison to the control group, IL-21R+ B cells were relatively lower in patients with stages I+II and those with fewer than 4 involved LNs. The intensity of IL-21 expression in T cells was associated with HER2 expression (P=0.029). Furthermore, we found that the majority of IL-21R+ B cells exhibited a naïve phenotype and most of IL-21+CD4+ T cells did not produce IFN-γ or IL-17. In conclusion, breast cancer from the early stages leads to a significant reduction in the proportion of peripheral CD4+ T cells. However, we did not find a significant change in IL-21 and its receptor expression during disease progression.
IL-21 是一种具有多种抗肿瘤和促肿瘤活性的细胞因子。它主要由 CD4+T 细胞产生,B 细胞是其关键靶点之一。在这项研究中,我们评估并比较了乳腺癌患者和健康个体外周血中 CD4+T 细胞和 B 细胞的 IL-21 表达。从患者和对照组采集血样。使用 Ficoll-Hypaque 密度梯度离心分离单核细胞。然后用抗 CD19/抗 IL-21R 或抗 CD4/抗 IL-21 抗体对这些分离的细胞进行染色,并使用流式细胞术进行分析。结果表明,患者和对照组之间 IL-21R+B 细胞和 IL-21+CD4+T 细胞的百分比没有显著差异。然而,乳腺癌患者的 CD4+T 细胞百分比显著下降(P=0.003)。这种下降发生在淋巴结(LN)受累之前的早期。与对照组相比,I+II 期和 LN 受累少于 4 个的患者 IL-21R+B 细胞相对较低。T 细胞中 IL-21 的表达强度与 HER2 表达相关(P=0.029)。此外,我们发现大多数 IL-21R+B 细胞表现出幼稚表型,大多数 IL-21+CD4+T 细胞不产生 IFN-γ 或 IL-17。总之,乳腺癌从早期开始就导致外周血 CD4+T 细胞比例显著减少。然而,我们没有发现疾病进展过程中 IL-21 和其受体表达的显著变化。