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Differentiation induced by physiological and pharmacological stimuli leads to increased antigenicity of human neuroblastoma cells

Author:
  • Lena-Maria Carlson
  • Sven Påhlman
  • Anna De Geer
  • Per Kogner
  • Jelena Levitskaya
Publishing year: 2008
Language: English
Pages: 398-411
Publication/Series: Cell Research
Volume: 18
Issue: 3
Document type: Journal article
Publisher: Science Press

Abstract english

Sympathetic neuronal differentiation is associated with favorable prognosis of neuroblastoma (NB), the most common extra-cranial solid tumor of early childhood. Differentiation agents have proved useful in clinical protocols of NB treatment, but using them as a sole treatment is not sufficient to induce tumor elimination in patients. Therefore, complementary approaches, such as immunotherapy, are warranted. Here we demonstrate that differentiation of NB cell lines and ex vivo isolated tumor cells in response to physiological or pharmacological stimuli is associated with acquisition of increased antigenicity. This manifests as increased expression of surface major histocompatibility class I complexes and ICAM-1 molecules and translates into increased sensitivity of NB cells to lysis by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. The latter is paralleled by enhanced ability of differentiated cells to form immune conjugates and bind increased amounts of granzyme B to the cell surface. We demonstrate, for the first time, that, regardless of the stimulus applied, the differentiation state in NBs is associated with increased tumor antigenicity that enables more efficient elimination of tumor cells by cytotoxic lymphocytes and paves the way for combined application of differentiation-inducing agents and immunotherapy as an auxiliary approach in NB patients.

Keywords

  • Cancer and Oncology
  • MHC
  • cytotoxic lymphocytes
  • antigenicity
  • neuroblastoma
  • differentiation

Other

Published
  • ISSN: 1748-7838
Sven Påhlman
E-mail: sven [dot] pahlman [at] med [dot] lu [dot] se

Professor

Division of Translational Cancer Research

+46 46 222 64 21

MV406 312K1

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