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

• Published in: PloS one Vol. 9; no. 12; p. e110378
• Main Authors: Fujita, Yohei, Okamoto, Masato, Goda, Hiroyuki, Tano, Tomoyuki, Nakashiro, Koh-ichi, Sugita, Atsuro, Fujita, Tomonobu, Koido, Shigeo, Homma, Sadamu, Kawakami, Yutaka, Hamakawa, Hiroyuki
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.12.2014; Public Library of Science (PLoS)
• Subjects: Aged; Aged, 80 and over; Antigens, CD - blood; Antigens, Differentiation, Myelomonocytic - blood; Biology and Life Sciences; Cancer therapies; Carcinoma, Squamous Cell - diagnosis; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - surgery; CD163 antigen; Clinical outcomes; Cytokines; Design of experiments; Disease-Free Survival; Enzyme-Linked Immunosorbent Assay; Experimental design; Female; Flow Cytometry; Gene Expression Regulation, Neoplastic; Head & neck cancer; Hospitals; Humans; Immune system; Immunohistochemistry; Immunology; Immunotherapy; Infiltration; Interleukin; Interleukin 10; Interleukin 8; Interleukin-10 - metabolism; Interleukin-8 - blood; Invasiveness; Liver cancer; Lymphocytes; Macrophages; Male; Maxillofacial surgery; Medical prognosis; Medical research; Medicine; Medicine and Health Sciences; Metastases; Metastasis; Middle Aged; Monocytes; Mouth Neoplasms - diagnosis; Mouth Neoplasms - metabolism; Mouth Neoplasms - surgery; Multivariate Analysis; Neutrophils; Oral cancer; Oral squamous cell carcinoma; Ovarian cancer; Patients; Peripheral blood; Prognosis; Prostate; Receptors, Cell Surface - blood; Squamous cell carcinoma; Surgery; Tissues; Treatment Outcome; Tumors; University graduates; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0110378

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