脑肿瘤患者粘膜相关不变 T 细胞水平及其与肿瘤免疫状态的相关性分析

BioSight Pub Date : 2024-01-15 DOI:10.46568/bios.v5i1.185
Barha Latif, Hafiz Muhammad, Haseeb Khaliq, Asad Ullah, Khawar Anwar, Adnan Arshad, Kausar Abdullah, Malik
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引用次数: 0

摘要

导言:原发性脑肿瘤是指由中枢神经系统内的细胞引起的一组异质性肿瘤,可以是良性的,也可以是恶性的。近年来,实验证据表明,尽管存在血脑屏障(BBB)且缺乏离散的淋巴组织,但脑实质内仍存在免疫功能细胞(TILs-肿瘤浸润淋巴细胞)。这些细胞中有许多是被称为 CD8+ 黏膜相关不变 T(MAIT)细胞的 T 淋巴细胞,它们会在刺激下增殖,在体外对肿瘤细胞具有细胞毒性。目的:通过对非传统 MAIT 细胞的三个定义标记 CD3D、KLRB1(CD161)和 TCR a 链变体 Va7.2(TRAV1-2 基因)的表达分析,评估非传统 MAIT 细胞在脑肿瘤中的频率。研究方法研究包括收集选定人群的 EDTA 血液样本和新鲜脑组织活检样本,然后提取 RNA 并合成 cDNA,以测量血液和组织样本中的相对表达分析。通过半定量实时 PCR 生成表达数据。结果研究结果表明,与组织样本相比,患者血液中 CD3D、KLRB1 (CD161) 和 TCR a 链变体 Va7.2 (TRAV1-2 基因) 的表达水平较高,表明这些 MAIT 细胞在病变组织中几乎没有转移。此外,随着肿瘤的发展,血液和组织样本中被研究基因的表达量都在下降。结论肿瘤微环境中的 MAIT 细胞可能会因长期激活而耗竭。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Analysis of Mucosal- Associated Invariant T Cell Levels And Their Correlation With Tumor Immune Status In Patients With Brain Tumors
Introduction: Primary brain tumors refer to a heterogeneous group of tumors arising from cells within the CNS, and can be benign or malignant. In recent years, experimental evidence suggests that, despite the presence of blood-brain barrier (BBB) and lack of discrete lymphoid tissue, there are immunocompetent cells (TILs-Tumor infiltrating lymphocytes) within the brain parenchyma. Many of these cells are T-Lymphocytes known as CD8+ Mucosal-associated invariant T (MAIT) cells, which proliferate with stimulation, and are cytotoxic to tumor cells in vitro. To evaluate the frequency of unconventional MAIT cells in the setting of brain tumors by expression analysis of their three defining markers CD3D, KLRB1 (CD161) and a TCR a-chain variant Va7.2 (TRAV1-2 gene). Methodology: The study involved collecting EDTA blood samples and fresh brain tissue biopsies from selected population followed by RNA extraction and cDNA synthesis for measurement of relative expression analysis in blood and tissues samples. Expression data was generated by semi-quantitative real time PCR. Results: The outcome of this study demonstrated higher expression level of  CD3D, KLRB1 (CD161) and a TCR a-chain variant Va7.2 (TRAV1-2 gene) in the blood of patients compared to the tissue samples showed little to no transmigration of these MAIT cells in the diseased tissues. Also, the expression of genes under-investigation was observed decreasing in both blood and tissue samples with the progression of tumor. Conclusion: MAIT cells might undergo depletion in the tumor micro-environment due to chronic activation induced exhaustion of these cells.
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