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.
Highlights
Head and neck squamous cell carcinoma (HNSCC) represents the fifth most frequently occurring cancer worldwide
Since the infiltration of CD163-positive cells into the tumor invasive front (CD163(IF)) but not the intra-tumor site (CD163(IT)) was strongly correlated with clinical outcomes (Overall survival [overall survival (OS)] and disease-free survival [DFS]) of the oral squamous cell carcinoma (OSCC) patients as described below, we present only the data of CD163 (IF)
We found no significant relationship between age, gender, TNM classification, histological differentiation, mode of cancer invasion, or primary site with serum IL-8, IL-8(T) and CD163(IF)
Summary
Head and neck squamous cell carcinoma (HNSCC) represents the fifth most frequently occurring cancer worldwide. Of the 1.6 million diagnoses and 333,000 deaths each year worldwide due to HNSCC, one-half are localized in the oral cavity [oral squamous cell carcinoma (OSCC)] [1]. Despite recent advances in surgery, radiotherapy and chemotherapy, the 5-year survival rate for patients with OSCC has remained at 50% for the past 30 years [2]. The treatment for patients with early-stage OSCC (Stage I or II) as well as for those with advanced OSCC (Stage III or IV) is mainly surgical resection. Tumor-Node-Metastasis (TMN) classification-based staging is an important prognostic factor in OSCC patients, the prognosis is not satisfactory even in early-stage patients, and high-risk patients who are Stage I/II OSCC might be missed based on the TNM staging [3,4,5,6]
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