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

Background and purpose As a proinflammatory factor, interleukin-17 (IL-17) can play a role in both tumor promotion and suppression. IL-17 is traditionally regarded as secreting mainly by CD4⁺ T helper cells (Th17 cells), while other immune subsets have been proved to produce IL-17, called IL-17⁺ cells. Considerable studies have drawn controversial conclusions about association between IL-17⁺/Th17 cells and prognosis of cancer patients. This meta-analysis was performed to systematically and quantitatively analyze prognostic values of IL-17⁺ cells and Th17 cells in cancer patients.

Methods A comprehensive retrieval was conducted in Pubmed (MEDLINE) and EMBASE databases. Pooled risk ratios (RRs) or hazard ratios (HRs) and corresponding 95% confidence intervals (CI) were calculated to evaluate the prognostic values of IL-17⁺ cells and Th17 cells in cancer patients.

Results A total of 42 studies with 5039 patitents were included. High IL-17⁺ cells was significantly associated with tumor recurrence (RR = 4.23, 95% CI [1.58, 11.35]), worse disease free survival (DFS) (HR = 1.84, 95% CI [1.22, 2.77]) and overall survival (OS) (HR = 1.39, 95% CI [1.04, 1.87]), especially in cancers of digestive system. Besides, no significant difference was observed between high IL-17⁺ cells and histological grade, lymph node metastasis, tumor volume, clinical stages or distant metastasis. Moreover, there was no significant difference in OS between high and low Th17 cells in cancer patients (HR = 0.93, 95% CI [0.58, 1.49]).

Conclusions This meta-analysis suggests high IL-17⁺ cells could be an indicator for worse survival in patients with malignant cancers, especially with cancers of digestive system. Although high Th17 cells appears to have non-statistically significance on prognosis, more clinical studies should be implemented to investigate the underlying function of Th17 cells within tumor microenvironment. This study put forward a new insight for potential application of anti-IL-17 target therapy in cancer therapeutics.