在宫颈癌发生过程中，辅助性 T (Th)-17 细胞在癌症患者的外周血和肿瘤组织中积累。我们之前证明 Th17 细胞与治疗耐药以及宫颈癌转移和复发有关；然而，Th17 驱动的潜在机制尚未完全了解。在这里，我们使用微阵列发现Th17细胞诱导宫颈癌细胞的上皮间质转化（EMT）表型，并通过诱导microRNA miR-142-5p促进2D培养物和3D球体的迁移和侵袭。作为负责机制，我们将琥珀酸脱氢酶 (SDH) 复合物的亚基 C 和 D 确定为 miR-142-5p 的新靶点，并提供证据表明 Th17-miR-142-5p 依赖性降低的 SDHC 和 SDHD 介导的增强使用 SDHC 和 SDHD 的小干扰 RNA (siRNA) 以及 miR-142-5p 抑制剂对癌细胞的迁移和侵袭进行研究。一致的是，患者血清中琥珀酸含量高，与淋巴结转移相关，患者活检组织中 SDHD 表达减少，与 Th17 细胞数量增加相关。相应地，弱或阴性 SDHD 表达与原位 Th17/CD4 T 细胞比率 >43.90% 的组合与无复发生存率降低相关。总之，我们揭示了 Th17 细胞促进宫颈癌进展的先前未知的分子机制，并建议评估 Th17 细胞作为宫颈癌免疫治疗的潜在靶点。本文受版权保护。版权所有。

During cervical carcinogenesis, T-helper (Th)-17 cells accumulate in the peripheral blood and tumor tissues of cancer patients. We previously demonstrated that Th17 cells are associated with therapy resistance as well as cervical cancer metastases and relapse; however, the underlying Th17-driven mechanisms are not fully understood. Here, using microarrays, we found that Th17 cells induced an epithelial-to-mesenchymal transition (EMT) phenotype of cervical cancer cells, and promoted migration and invasion of 2D cultures and 3D spheroids via induction of microRNA miR-142-5p. As the responsible mechanism, we identified the subunits C and D of the succinate dehydrogenase (SDH) complex as new targets of miR-142-5p and provided evidence that Th17-miR-142-5p-dependent reduced expression of SDHC and SDHD mediated enhanced migration and invasion of cancer cells using small interfering RNAs (siRNAs) for SDHC and SDHD, and miR-142-5p inhibitors. Consistently, patients exhibited high levels of succinate in their serum associated with lymph node metastases, and diminished expression of SDHD in patient biopsies correlated with increased numbers of Th17 cells. Correspondingly, a combination of weak or negative SDHD expression and a ratio of Th17/CD4+ T cells >43.90% in situ was associated with reduced recurrence-free survival. In summary, we unraveled a previously unknown molecular mechanism by which Th17 cells promote cervical cancer progression, and suggest evaluation of Th17 cells as a potential target for immunotherapy in cervical cancer.This article is protected by copyright. All rights reserved.