Unlocking the potential of CD70 as a novel immunotherapeutic target for non-small cell lung cancer

Oncotarget. 2015 May 30;6(15):13462-75. doi: 10.18632/oncotarget.3880.

Abstract

Although normally restricted to activated T and B cells and mature dendritic cells, constitutive expression of CD70, a member of the tumor necrosis family, has been described in both hematological and solid tumors, where it increases tumor cell and regulatory T cell survival by signaling through its receptor, CD27.We have assessed the co-expression of CD70 and CD27 in non-small cell lung cancer (NSCLC) by immunohistochemistry to explore a correlation between expression of the protein and tumor histologic subtype, genetic aberrations and prognosis. Furthermore, we tested the ability of ARGX-110, a CD70-blocking antibody, to induce NK cell-mediated cytotoxicity.Our results revealed CD70 expression on the surface of both primary and metastatic NSCLC tumor cells and in the tumor microenvironment. Moreover, CD27-expressing tumor infiltrating lymphocytes were found adjacent to the tumor cells, suggesting active CD70-mediated signaling. Finally, we have shown that ARGX-110, has potent cytotoxic effects on CD70+ NSCLC cell lines.

Keywords: CD70; NSCLC; immunotherapy; targeted therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / pharmacology*
  • CD27 Ligand / biosynthesis*
  • CD27 Ligand / immunology
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Disease Progression
  • Humans
  • Immunization, Passive / methods
  • Immunohistochemistry
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Molecular Targeted Therapy
  • Signal Transduction
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / biosynthesis
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology

Substances

  • Antibodies, Monoclonal
  • CD27 Ligand
  • CD70 protein, human
  • Tumor Necrosis Factor Receptor Superfamily, Member 7