Neuroblastoma-derived IL-β1 modulates the chemokine receptor repertoire of human resting nk cells

Roberta Castriconi, Alessandra Dondero, Francesca Bellora, Lorenzo Moretta, Aurora Castellano, Franco Locatelli, Maria Valeria Corrias, Alessandro Moretta, Cristina Bottino

Research output: Contribution to journalArticle

Abstract

In this study, we show that neuroblastoma (NB) cell conditioning affects the chemokine receptor repertoire of human resting NK cells. In particular, NB cells upregulated the expression of CXCR4 and CXCR3 in all NK cells and downregulated CX3CR1 in the CD56dim subset. On the contrary, the expression of CXCR1 and CCR7 remained unaltered. The phenomenon was dependent on the release by NB cells of IL-β1, and rIL-β1 induced a chemokine receptor repertoire identical to that of NB-conditioned NK cells. The immune modulatory role of IL-β1 appears to be dose dependent because low amounts of the cytokine were sufficient to modulate CXCR4 and CX3CR1 expression, intermediate amounts modified that of CXCR3, and high amounts were necessary to downregulate the expression of the NKp30 activating receptor. Notably, a similar receptor modulation was observed in rTGFb2- conditioned NK cells. Finally, the analysis of NK cells from patients with stage 4 NB suggests that NB conditioning could exert in vivo an immune modulatory effect resembling that emerged from in vitro experiments. Altogether our data propose a novel tumor escape-mechanism based on the modulation of chemokine receptors that play pivotal roles in NK cells bone marrow homing, egress, or recruitment into peripheral tissues.

Original languageEnglish
Pages (from-to)5321-5328
Number of pages8
JournalJournal of Immunology
Volume190
Issue number10
DOIs
Publication statusPublished - May 15 2013

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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