Colorectal Cancer Progression Is Associated with Accumulation of Th17 Lymphocytes in Tumor Tissues and Increased Serum Levels of Interleukin-6

Abstract

Colorectal cancer is a significant worldwide health problem, and an altered immunoresponse plays an important role in colorectal tumorigenesis and cancer progression. T helper 17 (Th17) lymphocytes (a subgroup of CD4 + T cells), together with the related cytokines, such as interleukin (IL)-6 and IL-17A, participate in cancer-related immunity. In this study, we measured the percentage of Th17 cells in peripheral blood mononuclear cells (PBMCs) and the levels of IL-17A and IL-6 in serum samples or tumor tissues, prepared from 40 colorectal cancer patients (a median age of 75 years), 32 age-matched healthy controls (a median age of 74 years), and 30 young healthy controls (a median age of 26 years). The percentage of Th17 cells in PBMCs and the serum IL-6 levels were higher in cancer patients than those in elderly controls, and they were associated with tumor progression. Moreover, the percentage of Th17 cells and the serum IL-6 levels were higher in elderly healthy controls than those in young healthy controls. In contrast, serum IL-17A levels were similar in the cancer patients and the elderly controls, although its serum levels were higher than those in young controls. Importantly, Th17 cells were accumulated in the intratumor and peritumor regions. In conclusion, the percentage of Th17 cells and the serum IL-6 level are significantly increased with aging, and their higher levels are correlated with colorectal cancer progression. The percentage of Th17 cells in PBMCs and the serum IL-6 level are potential biomarkers for predicting disease progression.

Vitamin D, Inflammation, and Colorectal Cancer Progression: A Review of Mechanistic Studies and Future Directions for Epidemiological Studies

“…Serum levels of TNFa, IL1b, IL6, IL8, and IL17A are higher in patients with colorectal cancer compared with healthy controls (39,(68)(69)(70). IL6 is additionally associated with increased tumor size, tumor stage, metastases, and decreased survival (39).…”

Hedyotis diffusa Willd. extract suppresses proliferation and induces apoptosis via IL-6-inducible STAT3 pathway inactivation in human colorectal cancer cells

“…This association was highlighted by a study that measured the cytokine levels in the sera of CRC patients and identified a direct correlation between IL-6 expression levels and CRC progression (7). Furthermore, activation of the intracellular Janus kinase (JAK)/STAT3 signaling pathway by IL-6 results in the expression of various genes involved in cancer growth and development (8).…”

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.…”

“…In recently years, a growing body of studies has shown Prognostic values of IL-17 + /Th17 cells in cancers: a meta-analysis 5 IL-17-producting cells (IL-17 + cells) are extensively existed in various inflammation-related cancers, such as lung cancer, hepatocellular carcinoma (HCC), colorectal cancer (CRC) and breast cancer [16][17][18][19]. More infiltration of IL-17 + cells was founded in intratumor tissues than that in peritumor nontumor tissues [20,21].…”