2 feb. 2012

El póster de Elena Catalán "MHC class I modulation due to metabolic changes regulates tumor sensitivity to NK cells" el "V International Conference BIFI 2012"

Elena Catalán perteneciente al equipo del Consorcio CliNK es becaria pre-doctoral del Ministerio de Ciencia e Innovación y ha realizado el póster titulado "MHC class I modulation due to metabolic changes regulates tumor sensitivity to NK cells" que estará durante el "V International Conference BIFI 2012" “Protein Targets: Discovery of Bioactive Compounds”


Elena Catalán, Juan Ignacio Aguiló, Seyma Charni,
Javier Naval, Martín Villalba, Julián Pardo & Alberto Anel

MHC class I modulation due to metabolic
changes regulates tumor sensitivity to NK cells
Tumoral cells have a tendency, known as "the Warburg effect", to use glycolysis to obtain energy instead of mitochondrial oxidative phosphorylation. In a previous work of our groups, it was demonstrated that, at least in leukemic cells, this glycolytic phenotype correlated with loss of ERK5 expressio and/or activity and, in consequence, with reduced MHC class I expression levels. Those results suggested that this mechanism could be used by tumoral cells to evade immunosurveillance, since lower MHC-I expression should result in lower sensitivity to cytotoxic T lymphocyte (CTL) control. However, the same scenario can also result in increase to NK cell-mediated control, as clearly demonstrated in leukemic cells in which ERK5 was eliminated by genetic means and MHC-I expression substantially reduced. In the present study, we have evaluated these outcomes, in vivo and in vitro, using the murine leukemia EL4 and the derived EL4-rº cell line, and also dietetic intervention on EL4 cells. EL4-rº cells are devoid of mitochondrial DNA and should be considered as an extreme case of the Warburg effect, since they are completely dependent on glycolysis for survival. While EL4-rº cells were equally sensitive to cytotoxicity exerted by CTL, they were more sensitive to activated NK cell mediated cytotoxicity exerted through the perforin/granzyme system. The increase in MHC-I expression induced by diclhoroacetate (DCA) in EL4 cells by forcing mitochondrial respiration resulted in turn in a decrease in sensitivity to activated NK cell cytotoxicity. These results correlate with the reduced ability of EL4-rº cells to generate tumors in syngeneic mice as compared with parental EL4 cells. Our present results show on one hand the importance of NK cells in immune antitumor surveillance, and on the other that the glycolytic phenotype of tumor cells does not seem to confer them an advantage in the context of immunosurveillance.

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