Prognostic significance of interleukin-8 and CD163-positive cell-infiltration in tumor tissues in patients with oral squamous cell carcinoma

PLoS One. 2014 Dec 2;9(12):e110378. doi: 10.1371/journal.pone.0110378. eCollection 2014.

Abstract

Purpose: We investigated whether serum interleukin (IL)-8 reflects the tumor microenvironment and has prognostic value in patients with oral squamous cell carcinoma (OSCC).

Experimental design: Fifty 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.

Results: We 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.

Conclusions: These 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, CD / blood*
  • Antigens, Differentiation, Myelomonocytic / blood*
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / surgery
  • Disease-Free Survival
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Interleukin-10 / metabolism
  • Interleukin-8 / blood*
  • Male
  • Middle Aged
  • Mouth Neoplasms / diagnosis
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / surgery
  • Multivariate Analysis
  • Prognosis
  • Receptors, Cell Surface / blood*
  • Treatment Outcome

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • CXCL8 protein, human
  • Interleukin-8
  • Receptors, Cell Surface
  • Interleukin-10

Grants and funding

This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Cultures, Sports, Science and Technology of Japan (No. 25293412) (http://www.mext.go.jp/english/) (HH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.