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

Carlson, Lena-Maria; Påhlman, Sven LU ; De Geer, Anna; Kogner, Per and Levitskaya, Jelena (2008) In Cell Research 18(3). p.398-411
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
MHC, cytotoxic lymphocytes, antigenicity, neuroblastoma, differentiation
in
Cell Research
volume
18
issue
3
pages
398 - 411
publisher
Science Press
external identifiers
  • wos:000255101000010
  • scopus:40249098578
ISSN
1748-7838
DOI
10.1038/cr.2008.27
language
English
LU publication?
yes
id
22f4fd04-f3af-48aa-90ff-ec3797972d6e (old id 1206474)
date added to LUP
2008-09-19 14:14:28
date last changed
2017-01-01 05:15:46
@article{22f4fd04-f3af-48aa-90ff-ec3797972d6e,
  abstract     = {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.},
  author       = {Carlson, Lena-Maria and Påhlman, Sven and De Geer, Anna and Kogner, Per and Levitskaya, Jelena},
  issn         = {1748-7838},
  keyword      = {MHC,cytotoxic lymphocytes,antigenicity,neuroblastoma,differentiation},
  language     = {eng},
  number       = {3},
  pages        = {398--411},
  publisher    = {Science Press},
  series       = {Cell Research},
  title        = {Differentiation induced by physiological and pharmacological stimuli leads to increased antigenicity of human neuroblastoma cells},
  url          = {http://dx.doi.org/10.1038/cr.2008.27},
  volume       = {18},
  year         = {2008},
}