髓源性抑制细胞和调节性 T 细胞共享共同的免疫调节途径相关 microRNAs，这些 microRNAs 受到急性淋巴细胞白血病和化疗的失调调控。
Myeloid-derived suppressor cells and regulatory T cells share common immunoregulatory pathways-related microRNAs that are dysregulated by acute lymphoblastic leukemia and chemotherapy.
机构信息
Immunology and Biotechnology Unit, Department of Zoology, Faculty of Science, Tanta University, Tanta, Egypt; Center of Excellence in Cancer Research, Tanta University Teaching Hospital, Tanta University, Tanta, Egypt.
Center of Excellence in Cancer Research, Tanta University Teaching Hospital, Tanta University, Tanta, Egypt; Department of Zoology, Faculty of Science, Damanhur University, Damanhur, Egypt.
出版信息
Hum Immunol. 2021 Jan;82(1):36-45. doi: 10.1016/j.humimm.2020.10.009. Epub 2020 Nov 6.
BACKGROUND
Relapse remains a critical challenge in children with acute lymphoblastic leukemia (ALL). The emergence of immunoregulatory cells, including myeloid-derived suppressor cells (MDSCs), and T regulatory (T) cells, has been considered one potential mechanism of relapse in children with ALL.
AIM
This study aimed to address the microRNAs (miRNAs) related to MDSCs and T cells and to explore their targeted immunoregulatory pathways.
METHODS
Affymetrix microarray was used for global miRNA profiling in B-ALL pediatric patients before, during, and after induction of chemotherapy. Bioinformatics analysis was performed on MDSCs and T cells-related dysregulated miRNAs, and miR-Pathway analysis was performed to explore their targeted immunoregulatory pathways.
RESULTS
516 miRNAs were dysregulated in ALL patients as compared to the healthy donor. Among them, 13 miRNAs and 8 miRNAs related to MDSCs and T cells, respectively, were common in all patients. Besides, 12 miRNAs were shared between MDSCs and T cells; 4 of them were common in all patients. Four immune-related pathways; TNF, TGF-β, FoxO, and Hippo were found implicated.
CONCLUSION
Our pilot study concluded certain miRNAs related to MDSCs and T cells, these miRNAs were linked to immunoregulatory pathways. Our results open avenues for testing those miRNA as molecular biomarkers for the immunosuppressive tumor microenvironment.
背景
复发仍然是儿童急性淋巴细胞白血病（ALL）的一个关键挑战。免疫调节细胞的出现，包括髓源性抑制细胞（MDSCs）和调节性 T 细胞（Tregs），被认为是 ALL 患儿复发的一个潜在机制。
目的
本研究旨在探讨与 MDSCs 和 T 细胞相关的 microRNAs（miRNAs）及其靶向免疫调节途径。
方法
采用 Affymetrix 微阵列对诱导化疗前后的 B-ALL 儿科患者进行全 miRNA 谱分析。对 MDSCs 和 T 细胞相关失调 miRNAs 进行生物信息学分析，并进行 miR-Pathway 分析，以探讨其靶向免疫调节途径。
结果
与健康供体相比，ALL 患者中有 516 个 miRNAs 失调。其中，有 13 个 miRNAs 与 MDSCs 相关，有 8 个 miRNAs 与 T 细胞相关，所有患者均有共同表达。此外，有 12 个 miRNAs 在 MDSCs 和 T 细胞之间共有，其中 4 个在所有患者中共同表达。发现有 4 个免疫相关途径，即 TNF、TGF-β、FoxO 和 Hippo 涉及其中。
结论
我们的初步研究得出了某些与 MDSCs 和 T 细胞相关的 miRNAs，这些 miRNAs 与免疫调节途径有关。我们的研究结果为检测这些 miRNA 作为免疫抑制肿瘤微环境的分子生物标志物提供了依据。
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