Tumor-Associated Neutrophils as a New Prognostic Factor in Cancer: A Systematic Review and Meta-Analysis

PURPOSE: Tumor-associated neutrophils (TAN) have been reported in a variety of malignancies. We conducted an up-to-date meta-analysis to evaluate the prognostic role of TAN in cancer. METHOD: Pubmed, Embase and web of science databases were searched for studies published up to April 2013. Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated. The impact of neutrophils localization and primary antibody were also assessed. RESULTS: A total of 3946 patients with various solid tumors from 20 studies were included. High density of intratumoral neutrophils were independently associated with unfavorable survival; the pooled HRs were 1.68 (95%CI: 1.36–2.07, I(2) = 55.8%, p<0.001) for recurrence-free survival (RFS)/disease-free survival (DFS), 3.36 (95%CI: 2.08–5.42, I(2) = 0%, p<0.001) for cancer-specific survival (CSS) and 1.66 (95%CI: 1.37–2.01, I(2) = 70.5%, p<0.001) for overall survival (OS). Peritumoral and stromal neutrophils were not statistically significantly associated with survival. When grouped by primary antibody, the pooled HRs were 1.80 (95%CI: 1.47–2.22, I(2) = 67.7%, p<0.001) for CD66b, and 1.44 (95%CI: 0.90–2.30, I(2) = 45.9%, p = 0.125) for CD15, suggesting that CD66b positive TAN might have a better prognostic value than CD15. CONCLUSION: High levels of intratumoral neutrophils are associated with unfavorable recurrence-free, cancer-specific and overall survival.