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CD8+T 细胞上 TIM-3 与 TIGIT 或 2B4 的共表达增加与局部晚期鼻咽癌的不良预后相关。

Increased co-expression of TIM-3 with TIGIT or 2B4 on CD8+ T cells is associated with poor prognosis in locally advanced nasopharyngeal carcinoma.

机构信息

The Third Affiliated Teaching Hospital of Xinjiang Medical University, Affiliated Cancer Hospital, Urumqi, China; Key Laboratory of Cancer Immunoterapy and Radiotherapy, Chinese Academy of Medical Sciences, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China.

Xinjiang Key Laboratory of Oncology, Urumqi, Xinjiang, China; Key Laboratory of Oncology of Xinjiang Uyghur Autonomous Region, Urumqi, China.

出版信息

Biomol Biomed. 2023 Jul 3;23(4):584-595. doi: 10.17305/bb.2022.8562.

DOI:10.17305/bb.2022.8562
PMID:36913701
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10351092/
Abstract

The use of immune checkpoint inhibitors in malignant tumors improves patient outcomes. Because single-agent immune checkpoint blockade has a low objective response rate, it is meaningful to explore combined blockade of immune checkpoint receptors. We aimed to investigate the co-expression of TIM-3 with TIGIT or 2B4 on peripheral blood CD8+ T cells from patients with locally advanced nasopharyngeal carcinoma. The correlation between co-expression level and clinical characteristics and prognosis was studied to provide a basis for immunotherapy for nasopharyngeal carcinoma. Flow cytometry was used to detect TIM-3/TIGIT and TIM-3/2B4 co-expression on CD8+ T cells. The differences in co-expression between patients and healthy controls were analyzed. The correlation between co-expression of TIM-3/TIGIT or TIM-3/2B4 and the patient clinical characteristics and prognosis was examined. Also, the correlation between the TIM-3/TIGIT or 2B4 co-expression and other common inhibitory receptors was analyzed. We further validated our results using mRNA data from the Gene Expression Omnibus (GEO) database. TIM-3/TIGIT and TIM-3/2B4 co-expression was upregulated on peripheral blood CD8+ T cells from patients with nasopharyngeal carcinoma. They were both correlated with poor prognosis. There was a correlation between TIM-3/TIGIT co-expression and patient age and pathological stage, whereas TIM-3/2B4 co-expression correlated with age and sex. CD8+ T cells with elevated mRNA levels of TIM3/TIGIT and TIM3/2B4 also showed increased expression of multiple inhibitory receptors, indicating T cell exhaustion in locally advanced nasopharyngeal carcinoma. TIM-3/TIGIT or TIM-3/2B4 can be used as potential targets for combination immunotherapy in locally advanced nasopharyngeal carcinoma.

摘要

免疫检查点抑制剂在恶性肿瘤中的应用改善了患者的预后。由于单药免疫检查点阻断的客观反应率较低，因此探索免疫检查点受体的联合阻断具有重要意义。我们旨在研究局部晚期鼻咽癌患者外周血 CD8+T 细胞中 TIM-3 与 TIGIT 或 2B4 的共表达情况。研究共表达水平与临床特征和预后的相关性，为鼻咽癌的免疫治疗提供依据。采用流式细胞术检测 CD8+T 细胞上 TIM-3/TIGIT 和 TIM-3/2B4 的共表达。分析患者与健康对照者之间的共表达差异。分析 TIM-3/TIGIT 或 TIM-3/2B4 共表达与患者临床特征和预后的相关性，并分析 TIM-3/TIGIT 或 2B4 共表达与其他常见抑制性受体的相关性。我们进一步使用基因表达综合数据库（GEO）中的 mRNA 数据验证了我们的结果。TIM-3/TIGIT 和 TIM-3/2B4 在鼻咽癌患者外周血 CD8+T 细胞上的共表达上调，与预后不良相关。TIM-3/TIGIT 共表达与患者年龄和病理分期相关，而 TIM-3/2B4 共表达与年龄和性别相关。TIM3/TIGIT 和 TIM3/2B4 mRNA 水平升高的 CD8+T 细胞也表现出多个抑制性受体的表达增加，表明局部晚期鼻咽癌中 T 细胞衰竭。TIM-3/TIGIT 或 TIM-3/2B4 可作为局部晚期鼻咽癌联合免疫治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42b8/10351092/a4bff0585fd6/bb-2023-8562f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42b8/10351092/72f17538d055/bb-2023-8562f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42b8/10351092/00fd5fb7004c/bb-2023-8562f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42b8/10351092/0df424bbdbef/bb-2023-8562f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42b8/10351092/a4bff0585fd6/bb-2023-8562f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42b8/10351092/72f17538d055/bb-2023-8562f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42b8/10351092/00fd5fb7004c/bb-2023-8562f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42b8/10351092/0df424bbdbef/bb-2023-8562f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42b8/10351092/a4bff0585fd6/bb-2023-8562f4.jpg

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