Non-small cell lung cancer induces an immunosuppressive phenotype of dendritic cells in tumor microenvironment by upregulating B7-H3

J Thorac Oncol. 2011 Jul;6(7):1162-8. doi: 10.1097/JTO.0b013e31821c421d.

Abstract

Introduction: Tumors may shift the phenotype and function of dendritic cells (DC) toward the induction of tolerance. In the status of full maturity, DC express a multitude of T cell costimulatory molecules enabling them to induce immune reactions, whereas nonactivated resident DC lack these T cell stimulating capacities. Therefore, we investigated the changes in DC phenotype and expression of B7-H molecules induced by non-small cell lung cancer (NSCLC).

Methods: The expression of T cell coinhibitory B7 molecules (B7-DC, B7-1, B7-2, B7-H1, B7-H3) on DC isolated from malignant and nonmalignant lung and lymph node tissue from patients attending curative surgery for NSCLC (n = 12) was analyzed. T cell stimulatory functions of DC isolated from malignant and nonmalignant lung and lymph node tissue samples were measured by allogeneic mixed lymphocyte reactions. Furthermore, the secretion of IL-10 and IL-12p40 by DC was analyzed (enzyme-linked immunosorbent assay).

Results: : B7-H3 was significantly upregulated in tumor-residing DC, whereas the expression of other B7 molecules, such as B7-DC, B7-1, B7-2, B7-H1, remained unchanged. Significantly reduced levels of T cell proliferation in mixed lymphocyte reactions with tumor-derived DC were recorded. Moreover, elevated concentrations of IL-10 were measured in tumor-derived DC, whereas IL-12 levels were reduced.

Conclusion: Our data indicate that (1) DC derived from NSCLC are immunosuppressive, and (2) under tumor conditions the coinhibitory molecule B7-H3 plays a crucial role in mediating the T cell suppressive effects of DC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • B7 Antigens / metabolism*
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • Flow Cytometry
  • Humans
  • Immunosuppression*
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Lymphocyte Activation
  • Phenotype
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology
  • Tumor Microenvironment

Substances

  • B7 Antigens
  • CD276 protein, human
  • Cytokines