ABCC3 expressed by CD56dim CD16+ NK cells predicts response in glioblastoma patients treated with combined chemotherapy and dendritic cell immunotherapy

Serena Pellegatta, Natalia Di Ianni, Sara Pessina, Rosina Paterra, Elena Anghileri, Marica Eoli, Gaetano Finocchiaro

Research output: Contribution to journalArticle

Abstract

Recently, we found that temozolomide (TMZ) can upregulate the expression of the multidrug-resistance protein ABCC3 in NK cells from both glioma-bearing mice and glioblastoma patients treated with dendritic cell immunotherapy combined with TMZ, allowing NK cells to escape apoptosis and favoring their role as antitumor effector cells. Here, we demonstrate that CD56dim NK cells expressing CD16+ are predominant in patients surviving more than 12 months after surgery without disease progression. CD56dim CD16+ NK cells co-expressed high levels of ABCC3 and IFN-γ. Notably, not only basal but also TMZ-induced ABCC3 expression was related to a strong, long-term NK cell response and a better prognosis of patients. The identification of the single nucleotide polymorphism (SNP) rs35467079 with the deletion of a cytosine (−897DelC) in the promoter region of the ABCC3 gene resulted associated with a better patient outcome. ABCC3 expression in patients carrying DelC compared to patients with reference haplotype was higher and modulated by TMZ. The transcription factor NRF2, involved in ABCC3 induction, was phosphorylated in CD56dim CD16+ NK cells expressing ABCC3 under TMZ treatment. Thus, ABCC3 protein and the SNP −897DelC can play a predictive role in patients affected by GBM, and possibly other cancers, treated with dendritic cell immunotherapy combined with chemotherapy.

Original languageEnglish
Article number5886
JournalInternational Journal of Molecular Sciences
Volume20
Issue number23
DOIs
Publication statusPublished - Dec 1 2019

    Fingerprint

Keywords

  • ABCC3
  • Chemotherapy
  • Glioblastoma
  • NK cells
  • Resistance

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this