Mechanism of LINC01018/miR-182-5p/Rab27B in the immune escape through PD-L1-mediated CD8⁺ T cell suppression in glioma.

IF 5.7 2区生物学 Q1 BIOLOGY

Biology Direct Pub Date : 2025-05-21 DOI:10.1186/s13062-025-00651-w

Su Hu, Guoshuo Chen, Aiping Luo, Hailin Zhao, Dan Li, Biao Peng, Jike Du, Dongdong Luo

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引用次数: 0

Abstract

Background: Glioma is a malignant tumor associated with poorer prognosis. This study aims to elucidate the mechanism of LINC01018/miR-182-5p/Rab27B axis in PD-L1-mediated CD8⁺ T cell suppression in the progression of gliomas.

Methods: LINC01018, miR-182-5p, and Rab27B expression levels in glioblastoma tissues were measured. The proportion of infiltrating macrophages and monocytes and CD8⁺ T cell function were assessed. The relationship between miR-182-5p and Rab27B was analyzed. Glioma cell activity, invasion, and migration were measured. The expression of E-cadherin, N-cadherin, Vimentin, PD-L1, iNOS, and CD206 was determined. Glioma cell-derived EVs were isolated, and the co-localization of Rab27B and PD-L1 and the binding of Rab27B to PD-L1 were analyzed. The endocytosis of EVs by microglia was assayed. The impact of LINC01018/miR-182-5p/Rab27B on glioma growth was observed. The function of macrophages and CD8⁺ T cells in tumors was analyzed.

Results: Rab27B was downregulated, and infiltrating macrophages and monocytes were increased in glioblastoma. miR-182-5p inhibited Rab27B expression. Rab27B knockdown reverses the inhibitory effect of LINC01018 overexpression on glioma cell growth. Glioma cells-derived EVs with low Rab27B expression carried more PD-L1 to increase PD-L1 expression and M2 polarization in microglia. LINC01018 overexpression reduced macrophages in orthotopic tumors. CD8⁺ T cell numbers showed no significant difference, but TIM-3 increased and IFN-γ decreased. miR-182-5p inhibition enhanced the therapeutic effect of anti-PD-L1, which was reversed after glioma cell-derived EVs.

Conclusion: LINC01018 promotes PD-L1-mediated CD8⁺ T cell suppression via the miR-182-5p/Rab27B axis in glioma cell-derived EVs, thereby contributing to immune escape in gliomas.

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LINC01018/miR-182-5p/Rab27B通过pd - l1介导的CD8+ T细胞抑制在胶质瘤中的免疫逃逸机制

背景：神经胶质瘤是一种预后较差的恶性肿瘤。本研究旨在阐明LINC01018/miR-182-5p/Rab27B轴在pd - l1介导的CD8+ T细胞抑制胶质瘤进展中的作用机制。方法：检测胶质母细胞瘤组织中LINC01018、miR-182-5p、Rab27B的表达水平。观察巨噬细胞、单核细胞浸润比例及CD8+ T细胞功能。分析miR-182-5p与Rab27B的关系。测量胶质瘤细胞的活性、侵袭和迁移。检测E-cadherin、N-cadherin、Vimentin、PD-L1、iNOS、CD206的表达。分离胶质瘤细胞源性ev，分析Rab27B与PD-L1的共定位以及Rab27B与PD-L1的结合。观察小胶质细胞对ev的内吞作用。观察LINC01018/miR-182-5p/Rab27B对胶质瘤生长的影响。分析巨噬细胞和CD8+ T细胞在肿瘤中的功能。结果：胶质母细胞瘤中Rab27B表达下调，浸润性巨噬细胞和单核细胞增多。miR-182-5p抑制Rab27B的表达。Rab27B敲低逆转了LINC01018过表达对胶质瘤细胞生长的抑制作用。Rab27B低表达的胶质瘤细胞源性ev携带更多的PD-L1，增加了小胶质细胞中PD-L1的表达和M2极化。LINC01018过表达可减少原位肿瘤中的巨噬细胞。CD8+ T细胞数量差异无统计学意义，但TIM-3升高，IFN-γ降低。miR-182-5p抑制增强了抗pd - l1的治疗效果，在胶质瘤细胞来源的ev后，这种作用被逆转。结论：在胶质瘤细胞源性EVs中，LINC01018通过miR-182-5p/Rab27B轴促进pd - l1介导的CD8+ T细胞抑制，从而促进胶质瘤的免疫逃逸。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biology Direct 生物-生物学

CiteScore

6.40

自引率

10.90%

发文量

审稿时长

7 months

期刊介绍： Biology Direct serves the life science research community as an open access, peer-reviewed online journal, providing authors and readers with an alternative to the traditional model of peer review. Biology Direct considers original research articles, hypotheses, comments, discovery notes and reviews in subject areas currently identified as those most conducive to the open review approach, primarily those with a significant non-experimental component.