Abstract
IL-17A is an important proinflammatory cytokine which is frequently elevated in tumor microenvironment. However, the role of intratumoral IL-17A in solid tumors remains controversial. Herein, we conducted a meta-analysis to assess the prognostic impact of intratumoral IL-17A in patients with solid tumor. PubMed and EBSCO were searched to identify the studies evaluating the associations between intratumoral IL-17A measured by immunohistochemistry (IHC) and overall survival (OS) and disease-free survival (DFS) in solid tumors. A total of 2972 patients with solid tumor from 21 published studies were incorporated into this meta-analysis. We found that high level of intratumoral IL-17A was significantly associated with worse 3-year, 5-year OS and 1-year, 3-year DFS, but not with 1-year OS or 5-year DFS in solid tumors. In addition, in stratified analyses by cancer types, IL-17A overexpression was significantly associated with worse OS in hepatic carcinoma, but with improved OS in esophageal squamous cell carcinoma (ESCC). Furthermore, high IL-17A expression positively correlated with advanced TNM stage. In conclusion, High expression of intratumoral IL-17A leads to an unfavorable clinical outcome in majority of solid tumors, implicating IL-17A is a valuable biomarker for prognostic prediction of human solid malignances and targeting it may have a potential for effective treatment.
Highlights
Chronic inflammation is closely linked to cancer [1, 2], Recent study has demonstrated that cancerrelated inflammation promotes tumor development and progression through various mechanisms, including stimulating angiogenesis, promoting cell proliferation and survival, inducing gene mutation and subverting antitumor immune responses [3, 4]
We found that high level of intratumoral IL-17A was significantly associated with worse 3-year, 5-year overall survival (OS) and 1-year, 3-year disease-free survival (DFS), but not with 1-year OS or 5-year DFS in solid tumors
High expression of intratumoral IL-17A leads to an unfavorable clinical outcome in majority of solid tumors, implicating IL-17A is a valuable biomarker for prognostic prediction of human solid malignances and targeting it may have a potential for effective treatment
Summary
Chronic inflammation is closely linked to cancer [1, 2], Recent study has demonstrated that cancerrelated inflammation promotes tumor development and progression through various mechanisms, including stimulating angiogenesis, promoting cell proliferation and survival, inducing gene mutation and subverting antitumor immune responses [3, 4]. Interleukin-17A (IL-17A), which initially termed as cytotoxic T-lymphocyte-associated antigen (CTLA-8), is the founding member of IL-17 cytokine family [10, 11]. It is mainly produced by Th17 cells and by γδ T, natural killer and CD8+ T cells [12, 13], relying on STAT3 activation triggered by IL-23 [14]. High level of IL-17A within tumor was shown to associate with poor survival of several cancers [18,19,20,21]; whereas some other studies reported opposite results [22,23,24,25]. The potential of IL-17A as an effective biomarker in prognostic prediction and targeted therapy is necessary to be explored
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