B7-H3 in combination with regulatory T cell is associated with tumor progression in primary human non-small cell lung cancer

Int J Clin Exp Pathol. 2015 Nov 1;8(11):13987-95. eCollection 2015.

Abstract

B7-H3 belongs to the co-inhibitory B7 family and plays an important role in the adaptive immune response in regulating T cells. In human malignancies, B7-H3 is reported to be involved in tumor immune evasion. However, the detailed molecular mechanism of B7-H3 in tumor evasion remains unclear, particularly in non-small cell lung cancer (NSCLC). Regulatory T cells (Tregs) are known as a key player in the inhibition of immune mechanisms. The study demonstrated the correlation between B7-H3 on tumor cells and the number of Tregs in the tumor microenvironment in NSCLC. B7-H3 was examined in tumor tissues from 110 patients with NSCLC by immunohistochemical analysis. Forkhead box P3+ (FOXP3+) Tregs in those spencimens were also detected and numbered. Survival curves were drawn using the Kaplan-Meier method and compared by the log-rank test. High B7-H3 expression in tumor cells significantly correlated with male gender, squamous NSCLC, advanced stage and shorter overall survival (OS) (P = 0.035, P = 0.004, P = 0.037, P = 0.014, respectively). Meanwhile, FOXP3 expression in tumor-infiltrating lymphocytes (TILs) was associated with male gender, regional lymph node involvement, advanced stage and worse OS (P = 0.009, P = 0.015, P = 0.014, P = 0.034, respectively). Significant correlation was identified between the expression of B7-H3 and the number of FOXP3+ TILs (P = 0.013). Patients with B7-H3 high/FOXP3 high had poorer OS (P = 0.006), suggesting that B7-H3 and Tregs may play a cooperatively role in tumor immune evasion, leading to poor outcomes for NSCLC patients.

Keywords: B7-H3; non-small cell lung cancer; regulatory T cell; tumor immune evasion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7 Antigens / analysis*
  • Biomarkers, Tumor / analysis*
  • CD4 Lymphocyte Count
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Chi-Square Distribution
  • Disease Progression
  • Female
  • Forkhead Transcription Factors / analysis
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Risk Factors
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology
  • Time Factors
  • Tumor Escape*
  • Tumor Microenvironment

Substances

  • B7 Antigens
  • Biomarkers, Tumor
  • CD276 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors