Myeloid-derived suppressor cells and regulatory T cells share common immunoregulatory pathways-related microRNAs that are dysregulated by acute lymphoblastic leukemia and chemotherapy,Human Immunology

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Myeloid-derived suppressor cells and regulatory T cells share common immunoregulatory pathways-related microRNAs that are dysregulated by acute lymphoblastic leukemia and chemotherapy
Human Immunology ( IF 3.1 ) Pub Date : 2020-11-06 , DOI: 10.1016/j.humimm.2020.10.009
Mohamed Labib Salem ₁ , Abdel-Aziz A Zidan ₂ , Randa Ezz El-Din El-Naggar ₃ , Mohamed Attia Saad ₄ , Mohamed El-Shanshory ₅ , Usama Bakry ₆ , Mona Zidan ₇

Affiliation

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_reg) 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_reg 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_reg 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_reg cells, respectively, were common in all patients. Besides, 12 miRNAs were shared between MDSCs and T_reg 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_reg cells, these miRNAs were linked to immunoregulatory pathways. Our results open avenues for testing those miRNA as molecular biomarkers for the immunosuppressive tumor microenvironment.

中文翻译：

髓源性抑制细胞和调节性 T 细胞共享共同的免疫调节通路相关 microRNA，这些 microRNA 因急性淋巴细胞白血病和化疗而失调

背景

复发仍然是急性淋巴细胞白血病 (ALL) 儿童面临的严峻挑战。免疫调节细胞的出现，包括髓源性抑制细胞 (MDSC) 和 T 调节 (T _reg ) 细胞，被认为是儿童 ALL 复发的一种潜在机制。

目的

本研究旨在解决与 MDSC 和 T _reg细胞相关的 microRNA (miRNA)并探索它们的靶向免疫调节途径。

方法

Affymetrix 微阵列用于 B-ALL 儿科患者在化疗诱导之前、期间和之后的整体 miRNA 分析。对 MDSC 和 T _reg细胞相关失调的 miRNA进行生物信息学分析，并进行 miR-Pathway 分析以探索它们的靶向免疫调节途径。

结果

与健康供体相比，ALL 患者中有 516 种 miRNA 失调。其中，13个miRNAs和8个miRNAs分别与MDSCs和_Treg细胞相关，在所有患者中普遍存在。此外，MDSCs 和 T _reg细胞共有 12 种 miRNA ；其中4例在所有患者中都很常见。四种免疫相关通路；发现涉及 TNF、TGF-β、FoxO 和 Hippo。