Immunological and Clinicopathological Significance of MFG-E8 Expression in Patients with Oral Squamous Cell Carcinoma

Pathol Oncol Res. 2020 Apr;26(2):1263-1268. doi: 10.1007/s12253-019-00692-3. Epub 2019 Jun 29.

Abstract

Milk fat globule-epidermal growth factor 8 (MFG-E8) is a glycoprotein secreted by the activated macrophages and acts as a bridge between apoptotic cells and phagocytes. Aside from macrophages, a variety of malignant cells also express MFG-E8. The objective of this study is to elucidate the clinical relevance and significance of MFG-E8 in the tumor microenvironment (TME) of patients with oral squamous cell carcinoma (OSCC). We investigated MFG-E8 expression in 74 patients with OSCC by immunohistochemistry and evaluated the relationship between MFG-E8 expression and various clinicopathological factors including immune cell infiltration. MFG-E8 expression was detected in 34 of 74 (45.9%) patients with OSCC and a significant correlation was observed with levels of infiltrating T cells, macrophages, and immunosuppressive M2 macrophages. Furthermore, MFG-E8 expression was also associated with clinical stage, lymphatic/vascular invasion, and Ki-67+ tumor cells but not with survival. Our results suggest that MFG-E8 may play an important role in shaping the immune suppressive network in TME as well as tumor progression.

Keywords: Immune suppression; Milk fat globule-epidermal growth factor 8 (MFG-E8); Oral squamous cell carcinoma (OSCC); Tumor microenvironment (TME).

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Surface / biosynthesis*
  • Biomarkers, Tumor / analysis
  • Female
  • Head and Neck Neoplasms / immunology*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Middle Aged
  • Milk Proteins / biosynthesis*
  • Squamous Cell Carcinoma of Head and Neck / immunology*
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Tumor Microenvironment / immunology*

Substances

  • Antigens, Surface
  • Biomarkers, Tumor
  • MFGE8 protein, human
  • Milk Proteins