Fig 2: Reverse transcription-quantitative polymerase chain reaction analysis of the Th17-associated intracellular cytokines and transcription factors IL17, IL23 and ROR?t in tumors and controls. *P<0.05. IL, interleukin; ROR, RAR-related orphan receptor; Cq, quantification cycle.

Fig 3: Analysis of factors related to interleukin-17 (IL-17) according to ovarian cancer (OC) histopathological type. A, Occupancy ratio of Th17 and ?dT17 cells in PBMC of OC patients or healthy controls (HC). B, Immunodetection of IL-17A and programmed cell death 1 ligand 1 (PD-L1) in surgical tumor specimens from OC patients. C, Effect of IL-17 on PD-L1 expression, as detected by western blotting in OVSAHO and MCAS cell lines. D, IL-6 expression following stimulation with IL-17A (right), as determined by ELISA; untreated cells served as control (left). In A-D, lines in the middle of each box indicate the median value, and the lower and upper boundaries represent the 5th and 95th percentiles, respectively. E, STAT3 phosphorylation in MCAS cells evaluated 24 h after IL-17A stimulation by ELISA. *P < .05, **P < .01 (Mann-Whitney test). White circles in panel indicate outliers

Fig 4: Interleukin-6 (IL-6) and transforming growth factor beta (TGF-ß) phosphorylate STAT3 in naïve T cells. Naïve T cells are induced to differentiate into regulatory T cells by TGF-ß in the absence of IL-6. ROR-?t is activated to induce differentiation of the naïve T cells into Th17 cells, which produce IL-17 and TNF-a. Nuclear factor-?B (NF-?B) activated by IL-17 or TNF-a stimulation induces expression of IL-6, which phosphorylates STAT3 in cancer cells. These steps result in programmed cell death 1 ligand 1 (PD-L1) expression in ovarian cancer (OC) cells and reactivation of IL-6 and STAT3 through a positive feedback loop

Fig 5: Programmed cell death 1 ligand 1 (PD-L1) expression induced by interleukin-17A (IL-17A) and its inhibition by IL-6, phospho-signal transducer and activator of transcription (pSTAT3) and nuclear factor-?B (NF-?B) inhibitors. A, Expression of IL-17-related genes in MCAS cells following IL-17 stimulation in the presence of anti–IL-6 Ab (mAbIL-6), as determined by western blotting. B, Change in PD-L1 expression upon IL-17 stimulation in the presence of NF-?B inhibitor (BAY11-7082) and 0.1% DMSO, as determined by western blotting. C, Western blotting of changes in PD-L1 and pSTAT3 expression following IL-17 stimulation in the presence of STAT3 inhibitor (S31-201: 0, 50, 10 and 200 µg/mL). Investigation of the relationship between PD-L1, IL-6, Th17 and neutrophil-to-lymphocyte ratio (NLR). D, Correlation between IL-6 and PD-L1 mRNA levels in PBMC of ovarian cancer (OC) patients. E, Relationship between IL-6 mRNA and Th17 occupancy ratio in PBMC of OC patients. F,G, Relationship between NLR in preoperative blood collected from OC patients and Th17 occupancy ratio in PBMC (F) or plasma IL-6 protein level (G). Results in (D) to (G) were analyzed using Spearman's test and shaded ellipses represent 95% confidence level ((D) ? = 0.52, P = 0.0023; (D) ? = 0.51, P = 0.0098; (F) ? = 0.49, P = 0.0068; (G) ? = 0.48, P = 0.0184)