Tumour‐Infiltrating FoxP3+ and IL‐17‐Producing T Cells Affect the Progression and Prognosis of Gallbladder Carcinoma after Surgery

Abstract

Tumour-infiltrating lymphocytes (TILs) have been found to play crucial roles in a series of cancers. However, the impact of these cells on gallbladder carcinoma (GBC) remains poorly understood. In this study, we examined infiltrating FoxP3+, IL-17+, CD4+ and CD8+ cells by immunohistochemistry in specimens of 104 patients with GBC and evaluated the association of these cells with clinicopathological features and prognosis. The number of FoxP3+ cells was increased in a stepwise manner from CC to GA and GBC (GA versus CC, P = 0.036; early GBC versus GA, P = 0.032; advanced versus early GBC, P = 0.025). Both intratumoral FoxP3+ and IL-17+ cells correlated with nodal metastasis and TNM stage. Additionally, there were more infiltrating FoxP3+ cells in specimens with distant metastasis (P = 0.014). The group with high FoxP3+ cells showed poor overall survival (OS, P < 0.001) and disease-free survival (DFS, P < 0.001), and high infiltration of IL-17-producing cells was also a predictor of poor OS (P = 0.024). Multivariate analysis revealed that the presence of intratumoral FoxP3+ cells was an independent prognostic indicator for poor DFS (P < 0.01). In summary, these findings indicate that FoxP3+ and IL-17+ cells cooperatively facilitate pathogenesis and progression of GBC and show prognostic significance for OS or DFS.

IL17 producing γδT cells induce angiogenesis and are associated with poor survival in gallbladder cancer patients

“…Moreover, it is reported that Th17 and Treg frequently colocalize at the same anatomic compartments and mutually promote each other's generation and function . We observed the infiltration of Treg and IL17 producing cells in the tumor environment of GBC patients which corroborate the earlier observations in GBC patients reported by Zhang et al . This suggests that although the ratios of Tγδ17/Treg, Th17/Treg and Tc17/Treg were increased in GBC patients, IL17 producing cells and Tregs may act cooperatively and eventually contribute to the poor survival observed in GBC patients.…”

The correlations between IL-17 vs. Th17 cells and cancer patient survival: a systematic review

“…CLL D chronic lymphocytic leukemia; AC D adenocarcinoma; CRC D colorectal carcinoma; HCC D hepatocellular carcinoma; NA D not applicable or not mentioned in the article; NSCLC D non-small cell lung carcinoma. 15,16,[18][19][20]30,37,[40][41][42][43][44][45][46][47][48][49][50] Five studies reported on a correlation between a high number of IL-17 C cells and improved survival. 21,28,29,51,52 It is important to note that in two of these five studies, the IL-17 C cells were scored in areas with the densest lymphocytic infiltrate, one of which was on pancreatic ductal adenocarcinoma patients who had received immunotherapy (the correlation between IL-17 and survival was based on 12 patients).…”

Prognostic significances of interleukin-17-producing cells and Th17 cells in malignant cancers: a meta-analysis of the literatures

“…As shown in Fig 2.A, the relevance between high level of IL-17 + cells and histological grade (poor differentiation versus (vs.) well/moderate differentiation) was evaluated in 14 studies including head and neck cancers (HNC) (n = 2) [38,39], breast cancer (n = 1) [17], non-small-cell lung cancer (NSCLC) (n = 2) [40,41] and cancers of digestive system (n = 9) [16,20,28,[42][43][44][45][46][47], with 1645 patients. Results showed no statistical significance was found between high level of IL-17 + cells and histological grade (RR = 1.10, 95% CI [0.90, 1.34]).…”

“…The association between high IL-17 + cells and lymph node metastasis was explored in 9 studies with 1074 patients [17,20,38,[42][43][44][45][46]48] (Fig 2.B). RR for the relevant 9 studies was 0.97 (95% CI [0.81, 1.15]), indicating the high IL-17 + cells within tumor tissues had no significant influence on lymph node status.…”

“…The prognostic values of IL-17+ cells in tumor volume (T3/T4 vs. T1/T2 stages) (Fig 3.A) and clinical stage (III/IV vs. I/II stages) (Fig 3.B) were investigated in 8 studies Prognostic values of IL-17 + /Th17 cells in cancers: a meta-analysis 16 with 1036 patients [17,20,38,42,43,46,48,49] and 11 studies with 1370 patients [17,20,[40][41][42][43]45,46,[48][49][50] [40,41]. The random effect model was applied for analyses of tumor volume and clinical stages owing to the obvious heterogeneities (I 2 = 67.2%, p = 0.003 and I 2 = 73.9%, p < 0.001, respectively).…”