Invariant natural killer T infiltration in neuroblastoma with favorable outcome

Pediatr Surg Int. 2018 Feb;34(2):195-201. doi: 10.1007/s00383-017-4189-x. Epub 2017 Oct 10.

Abstract

Background: Tumor immunity has been suggested to play a key role in clinical and biological behavior of neuroblastomas. Given that CD1-restricted invariant natural killer T (iNKT) cells enhance both innate and acquired tumor immunity, we investigated the expression of the iNKT-cell-specific T-cell receptor Vα24-Jα18 in neuroblastoma tissues and its correlation with clinical and biological characteristics.

Methods: Using real- time quantitative PCR, we quantified the expression of Vα24-Jα18 in untreated tumor samples from 107 neuroblastoma cases followed in our institution and analyzed the correlation between the presence of infiltrated iNKT cells and clinical characteristics or patients' outcome.

Results: Vα24-Jα18 receptor was detected in 62 untreated cases (57.9%). The expression was significantly higher in stages 1, 2, 3, or 4S (P = 0.0099), in tumors with low or intermediate risk (P = 0.0050), with high TrkA expression (P = 0.0229), with favorable histology (P = 0.0026), with aneuploidy (P = 0.0348), and in younger patients (P = 0.0036). The overall survival rate was significantly higher in patients with iNKT-cell infiltration (log-rank; P = 0.0089).

Conclusions: Since tumor-infiltrating iNKT cells were predominantly observed in neuroblastomas undergoing spontaneous differentiation and/or regression, we suggest that iNKT cells might play a key role in these processes.

Keywords: Natural killer T cell; Neuroblastoma; Spontaneous regression; Tumor immunity; Tumor-infiltrating lymphocytes.

MeSH terms

  • Blotting, Southern
  • Child
  • Child, Preschool
  • DNA, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Infant
  • Infant, Newborn
  • Intestinal Mucosa
  • Male
  • N-Myc Proto-Oncogene Protein / biosynthesis
  • N-Myc Proto-Oncogene Protein / genetics*
  • Natural Killer T-Cells / metabolism
  • Natural Killer T-Cells / pathology*
  • Neuroblastoma / genetics*
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology
  • Real-Time Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell / biosynthesis
  • Receptors, Antigen, T-Cell / genetics*

Substances

  • DNA, Neoplasm
  • MYCN protein, human
  • N-Myc Proto-Oncogene Protein
  • Receptors, Antigen, T-Cell
  • Valpha24 protein, human