Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kawaramachi-hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
Department of Pediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.
Br J Cancer. 2024 Mar;130(4):671-681. doi: 10.1038/s41416-023-02532-3. Epub 2023 Dec 26.
Recent studies have identified that low levels of some tumour suppressor microRNAs (miRNAs) in the blood contribute to tumour progression and poor outcomes in various cancers. However, no study has proved these miRNAs are associated with cancer immune mechanisms.
From a systematic review of the NCBI and miRNA databases, four tumour suppressor miRNA candidates were selected (miR-5193, miR-4443, miR-520h, miR-496) that putatively target programmed cell death ligand 1 (PD-L1).
Test-scale and large-scale analyses revealed that plasma levels of miR-5193 were significantly lower in gastric cancer (GC) patients than in healthy volunteers (HVs). Low plasma levels of miR-5193 were associated with advanced pathological stages and were an independent prognostic factor. Overexpression of miR-5193 in GC cells suppressed PD-L1 on the surface of GC cells, even with IFN-γ stimulation. In the coculture model of GC cells and T cells stimulated by anti-CD3/anti-CD28 beads, overexpression of miR-5193 increased anti-tumour activity of T cells by suppressing PD-L1 expression. Subcutaneous injection of miR-5193 also significantly enhanced the tumour-killing activity and trafficking of T cells in mice.
Low blood levels of miR-5193 are associated with GC progression and poor outcomes and could be a target of nucleic acid immunotherapy in GC patients.
最近的研究表明，血液中某些肿瘤抑制 microRNA（miRNA）水平较低与多种癌症中的肿瘤进展和不良预后有关。然而，尚无研究证明这些 miRNA 与癌症免疫机制有关。
从 NCBI 和 miRNA 数据库的系统评价中，选择了四个肿瘤抑制 miRNA 候选物（miR-5193、miR-4443、miR-520h、miR-496），它们可能靶向程序性细胞死亡配体 1（PD-L1）。
测试规模和大规模分析显示，胃癌（GC）患者血浆中 miR-5193 的水平明显低于健康志愿者（HV）。低血浆 miR-5193 水平与晚期病理分期有关，是独立的预后因素。在 GC 细胞中过表达 miR-5193 可抑制 GC 细胞表面的 PD-L1，即使有 IFN-γ 刺激。在抗 CD3/抗 CD28 珠刺激的 GC 细胞和 T 细胞共培养模型中，过表达 miR-5193 通过抑制 PD-L1 表达增强了 T 细胞的抗肿瘤活性。miR-5193 的皮下注射也显著增强了小鼠中 T 细胞的杀伤活性和迁移。
低血液 miR-5193 水平与 GC 进展和不良预后有关，可能成为 GC 患者核酸免疫治疗的靶点。
