B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression

Clin Cancer Res. 2004 Aug 1;10(15):5094-100. doi: 10.1158/1078-0432.CCR-04-0428.

Abstract

Purpose: B7-H1/PD-L1 (B7-H1) and B7-DC/PD-L2 (B7-DC) are ligands for the receptor PD-1, which is known to negatively regulate T-cell activation. In the present study, we investigated the expression of B7-H1 and B7-DC in tumor specimens of non-small cell lung cancer and their relationships with clinicopathological variables and postoperative survival. Furthermore, we examined the correlation between B7-H1 expression on tumor cells and the number of tumor-infiltrating lymphocytes (TILs) or PD-1 expression on TILs.

Experimental design: The expression of B7-H1 and B7-DC in 52 surgically resected specimens of non-small cell lung cancer was evaluated immunohistochemically.

Results: Expression of B7-H1 and B7-DC was focally observed in all non-small cell lung cancer tumor specimens. No relationship was found between the expression of B7-H1 or B7-DC and clinicopathological variables or postoperative survival. However, in the same sections evaluated, significantly fewer TILs were identified in B7-H1-positive tumor regions than in B7-H1-negative tumor regions in a subset of five patients (P = 0.01). Moreover, the percentage of TILs expressing PD-1 was significantly lower in B7-H1-positive tumor regions than in B7-H1-negative tumor regions (P = 0.02).

Conclusions: The expression of B7-H1 on tumor cells in local areas reciprocally correlated with the number of TILs, and this may contribute to negative regulation in antitumor immune responses in non-small cell lung cancer.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD
  • Antigens, Surface / biosynthesis*
  • Antineoplastic Agents / pharmacology
  • Apoptosis Regulatory Proteins
  • B7-1 Antigen / biosynthesis*
  • B7-H1 Antigen
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / metabolism
  • Cell Line, Tumor
  • Female
  • Humans
  • Immunohistochemistry
  • Leukocyte Common Antigens / biosynthesis
  • Ligands
  • Lung Neoplasms / immunology
  • Lung Neoplasms / metabolism*
  • Lymphocyte Activation
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Male
  • Membrane Glycoproteins / biosynthesis*
  • Middle Aged
  • Peptides
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor
  • T-Lymphocytes / metabolism

Substances

  • Antigens, CD
  • Antigens, Surface
  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • B7-1 Antigen
  • B7-H1 Antigen
  • CD274 protein, human
  • Ligands
  • Membrane Glycoproteins
  • PDCD1 protein, human
  • PDCD1LG2 protein, human
  • Peptides
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor
  • Leukocyte Common Antigens