Analysis of B7-H4 expression in metastatic pleural adenocarcinoma and therapeutic potential of its antagonists

BMC Cancer. 2017 Sep 18;17(1):652. doi: 10.1186/s12885-017-3615-8.

Abstract

Background: The increasing incidence and poor outcome associated with malignant pleural effusion (MPE) requires finding an effective treatment for this disease. Inhibitory B7-H4 is expressed in many different human cancers but its role in malignant pleural tissue has yet to be established.

Methods: Here, patients with metastatic pleural adenocarcinoma (MPA) or with early-stage lung adenocarcinoma were clinically and statistically analyzed. Immunohistochemistry and confocal microscopy were used to determinate the expression of B7-H4 in the cancer cells. By using MPE model, we sought to a potential immunotherapy for MPE with anti-B7-H4 mAb.

Results: When compared to early-stage lung adenocarcinoma, MPA possessed higher level of nuclei membranous B7-H4 and lower cytoplasmic B7-H4 expression. Also, nuclei membranous B7-H4 expression was found to be positively correlated to Ki-67 expression, and indicated a possible poor prognosis of MPA. In mouse MPE model, intra-pleurally injection of anti-B7-H4 mAb effectively suppressed MPE formation.

Conclusions: Taken together, our data was in support of the significance of B7-H4 expression in MPA, which also suggest it warrants further exploration for potential immunotherapy of MPE.

Keywords: Adenocarcinoma; B7-H4; Immunotherapy; Metastatic pleural neoplasms.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / secondary
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Lewis Lung / drug therapy
  • Carcinoma, Lewis Lung / metabolism
  • Cell Line, Tumor
  • Cytoplasm / metabolism
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Mice, Inbred C57BL
  • Middle Aged
  • Neoplasm Transplantation
  • Nuclear Envelope / metabolism
  • Pleural Effusion, Malignant
  • Pleural Neoplasms / drug therapy
  • Pleural Neoplasms / metabolism*
  • Pleural Neoplasms / secondary
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1 / antagonists & inhibitors
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1 / metabolism*

Substances

  • Antineoplastic Agents
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1
  • VTCN1 protein, human