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ERK5 knockdown generates mouse leukemia cells with low MHC class I levels that activate NK cells and block

Seyma Charni1, Juan Ignacio Aguilo, Johan Garaude

  • 1Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5535, Université Montpellier 1 and 2, Montpellier, France;

Journal of Immunology (Baltimore, Md. : 1950)
|March 7, 2009
PubMed

Insights

Small hairpin RNA for ERK5 (shERK5) reduces ERK5 levels in leukemia cells, enhancing their elimination by NK cells and enabling their use as a novel tumor cell-based vaccine.

Area of Science:

  • Immunology
  • Cancer Research
  • Molecular Biology

Background:

  • Tumor cell-based vaccines are limited by poor immunogenicity due to cell extracts or apoptotic cells.
  • Live tumor cells possess greater antigen presentation potential if processed by the host immune system.

Purpose of the Study:

  • To investigate the impact of stable expression of small hairpin RNA for ERK5 (shERK5) on leukemia cell immunogenicity and tumor activity.
  • To evaluate the potential of shERK5-expressing leukemia cells as a tumor cell-based vaccine.

Main Methods:

  • Stable expression of shERK5 in human and mouse leukemic cells.
  • Assessment of ERK5 levels, MHC class I expression, and NK cell-mediated elimination.
  • In vivo studies involving coinjection and subcutaneous injection of shERK5-expressing cells with wild-type tumor cells.

Main Results:

  • shERK5 expression decreased ERK5 levels and led to NK cell-mediated elimination of leukemia cells in vivo.
  • shERK5-expressing cells exhibited down-regulated MHC class I expression.
  • Ectopic activation of the ERK5 pathway induced MHC class I gene expression.
  • Coinjection and subcutaneous injection of shERK5-expressing cells diminished the survival and tumor development of wild-type tumor cells.

Conclusions:

  • shERK5 expression attenuates the tumor activity of leukemia cells.
  • Leukemia cells engineered with shERK5 show potential for use as an effective tumor cell-based vaccine.

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