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.