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外周血 T 淋巴细胞中 IFNAR1 表达与结直肠癌患者炎症细胞因子、肿瘤浸润淋巴细胞和化疗敏感性的相关性。

Correlation between IFNAR1 expression in peripheral blood T lymphocytes and inflammatory cytokines, tumor-infiltrating lymphocytes, and chemosensitivity in patients with colorectal cancer.

机构信息

Department of General Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China; Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.

Department of Oncology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.

出版信息

Cytokine. 2022 Nov;159:156008. doi: 10.1016/j.cyto.2022.156008. Epub 2022 Sep 2.

Abstract

IFN-α receptor (IFNAR) is critical for maintaining the crosstalk between cancer cells and lymphocytes. We investigated IFNAR1 expression in peripheral blood CD4 and CD8 T cells and explored their relationships with plasma cytokines, chemosensitivity and infiltrated T cells in the tumor microenvironment (TME) of colorectal cancer (CRC). The levels of IFNAR1, IFN-γ, and PD1 in peripheral T cells were tested using flow cytometry. Immunohistochemical staining of IFNAR1 in CRC tissues was performed. A cytometric bead array was used to determine the plasma concentrations of cytokines. In CRC patients, IFNAR1 levels were significantly increased in peripheral blood T cells, and plasma IL-6 levels were also significantly increased. Pearson correlation analysis revealed that IFNAR1 expression in CD8 T cells was negatively associated with plasma IL-2, IFN-γ, and TNFα. IFNAR1 expression in CD4 T cells was positively associated with TME infiltrated levels of CD8 T cells. The levels of CD8 T cells with IFNAR1 and plasma IFN-γ were associated with chemosensitivity. Collectively, IFNAR1 levels in CD4 and CD8 T cells were significantly upregulated in CRC patients and positively associated with T-cell infiltration. IFNAR1 may be a chemotherapy biomarker for predicting response.

摘要

IFN-α 受体 (IFNAR) 对于维持癌细胞与淋巴细胞之间的串扰至关重要。我们研究了外周血 CD4 和 CD8 T 细胞中的 IFNAR1 表达,并探索了它们与结直肠癌 (CRC) 肿瘤微环境 (TME) 中血浆细胞因子、化学敏感性和浸润 T 细胞的关系。使用流式细胞术检测外周 T 细胞中的 IFNAR1、IFN-γ 和 PD1 水平。对 CRC 组织中的 IFNAR1 进行免疫组织化学染色。使用细胞因子检测试剂盒测定血浆细胞因子浓度。在 CRC 患者中,外周血 T 细胞中的 IFNAR1 水平显著升高,血浆 IL-6 水平也显著升高。Pearson 相关分析显示,CD8 T 细胞中 IFNAR1 的表达与血浆 IL-2、IFN-γ 和 TNFα 呈负相关。CD4 T 细胞中 IFNAR1 的表达与 TME 浸润的 CD8 T 细胞水平呈正相关。具有 IFNAR1 和血浆 IFN-γ 的 CD8 T 细胞水平与化学敏感性相关。总之,CRC 患者外周血 CD4 和 CD8 T 细胞中的 IFNAR1 水平显著上调,并与 T 细胞浸润呈正相关。IFNAR1 可能是预测反应的化疗生物标志物。

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