CXCR2-CXCL1 axis is correlated with neutrophil infiltration and predicts a poor prognosis in hepatocellular carcinoma

Background & aims: inflammation is a hallmark of cancer,yet the mechanisms that regulate immune cell infiltration into tumors remain poorly characterized. this study attempted to characterize the composition,distribution,and prognostic value of cxcr2+ cells in hepatocellular carcinoma (hcc) and to examine the cxcr2 ligands that are responsible for local immune infiltration in different areas of hcc tumors. methods: immunohistochemistry and immunofluorescene were used to identify cxcr2+ cells in hcc tissues. kaplan-meier analysis and cox regression models were applied to estimate recurrence-free survival (rfs) and overall survival (os) for 259 hcc patients. the expression levels of cxcr2 ligands (cxcl-1,-2,-5,and -8) were measured by real-time pcr and compared with local immune cell density. the combined prognostic value of the cxcr2-cxcl1 axis was further evaluated. results: in hcc tissues,cxcr2+ cells were mainly neutrophils that were enriched in the peri-tumoral stroma (ps) region. kaplan-meier survival analysis showed that increased cxcr2+ ps cells were associated with reduced rfs and os (p∈=∈0.015 for rfs; p∈=∈0.002 for os). multivariate cox proportional hazards analysis identified cxcr2+ ps cell density as an independent prognostic factor for os (hazard ratio [hr]∈=∈1.737,95 % confidence interval [ci]∈=∈1.167-2.585,p∈=∈0.006). furthermore,we detected a positive correlation between the density of cd15+ neutrophils and cxcl1 levels in both the peri-tumoral stroma and intra-tumoral regions. the combination of cxcr2 and cxcl1 expression levels represented a powerful predictor of a poor prognosis for patients with hcc. conclusions: our data showed that the cxcr2+ cell density was an independent prognostic factor for predicting os for hcc patients. the cxcr2-cxcl1 axis can regulate neutrophil infiltration into hcc tumor tissues and might represent a useful target for anti-hcc therapies. © 2015 li et al.