Prognostic Significance of Interleukin-8 and CD163-Positive Cell-Infiltration in Tumor Tissues in Patients with Oral Squamous Cell Carcinoma

Abstract

PurposeWe investigated whether serum interleukin (IL)-8 reflects the tumor microenvironment and has prognostic value in patients with oral squamous cell carcinoma (OSCC).Experimental DesignFifty OSCC patients who received radical resection of their tumor(s) were enrolled. Preoperative sera were measured for IL-8 by ELISA. Expression of IL-8 and the infiltration of immune cells in tumor tissues were analyzed by an immunohistochemical staining of surgical specimens.ResultsWe found that disease-free survival (DFS) was significantly longer in the Stage I/II OSCC patients with low serum IL-8 levels compared to those with high levels (p = 0.001). The tumor expression of IL-8, i.e., IL-8(T) and the density of CD163-positive cells in the tumor invasive front, i.e., CD163(IF) were correlated with the serum IL-8 level (p = 0.033 and p = 0.038, respectively), and they were associated with poor clinical outcome (p = 0.007 and p = 0.002, respectively, in DFS) in all patients. A multivariate analysis revealed that N status, IL-8(T) and CD163(IF) significantly affected the DFS of the patients. Further analysis suggested that combination of N status with serum IL-8, IL-8(T) or CD163(IF) may be a new criterion for discriminating between OSCC patients at high and low risk for tumor relapse. Interestingly, the in vitro experiments demonstrated that IL-8 enhanced generation of CD163-positive M2 macrophages from peripheral blood monocytes, and that the cells produced IL-10.ConclusionsThese findings indicate that IL-8 may be involved in poor clinical outcomes via generation of CD163-positive M2 macrophages, and that these factors in addition to N status may have prognostic value in patients with resectable OSCSS.

Proinflammatory cytokines as serum biomarker in oral carcinoma—A prospective multi‐biomarker approach

“…For IL‐8, Fujita et al demonstrated that disease‐free survival was significantly longer in the Stage I/II OSCC patients with low serum IL‐8 levels compared to those with high levels. The tumor expression of IL‐8 and the density of CD163‐positive cells in the tumor invasive front were associated with the serum IL‐8 level, and an increase was correlated with worse clinical outcome.…”

Protease-activated Receptor-2 (PAR-2)-mediated Nf-κB Activation Suppresses Inflammation-associated Tumor Suppressor MicroRNAs in Oral Squamous Cell Carcinoma

“…Interleukin 8 (CXCL8 gene, IL8 protein) is a member of the pro-inflammatory CXC chemokine gene family. Expression levels are elevated in the saliva of oral cancer patients, and high serum IL8 levels correlate with a poor clinical outcome in OSCC (41,42). The interleukin encoded by the IL1A gene is a potent mediator of inflammation and is involved in epidermal barrier function (43).…”

Gas6 protein induces invasion and reduces inflammatory cytokines in oral squamous cell carcinoma

“…IL‐8 is a cytokine involved in tumor growth and angiogenesis in a variety of malignancies . In fact, IL‐8 is differentially regulated, but often found to be increased in OSCC tumors . Decreased IL‐8 observed in these cells following Gas6 treatment could be attributed to poorly characterized functions of IL‐8 in tumor development.…”

“…29 In fact, IL-8 is differentially regulated, but often found to be increased in OSCC tumors. 30 Decreased IL-8 observed in these cells following Gas6 treatment could be attributed to poorly characterized functions of IL-8 in tumor development. Perhaps a specific role for IL-8 during tumor formation exists, but it is not necessarily required for invasion or metastasis of already transitioned OSCC cells.…”