Tumor cells have a tendency to use glucose fermentation to obtain energy instead of mitochondrial oxidative phosphorylation (OXPHOS). We demonstrated that this phenotype correlated with loss of ERK5 expression and with reduced MHC class I expression. Consequently, tumor cells could evade cytotoxic T lymphocyte (CTL)-mediated immune surveillance, but also increase their sensitivity to natural killer (NK) cells. These outcomes were evaluated using two cellular models: leukemic EL4 cells and L929 transformed fibroblasts and their derived ρ° cell lines, which lack mitochondrial DNA. We have also used a L929 cell sub-line that spontaneously lost matrix attachment (L929dt), reminiscent of metastasis generation, that also downregulated MHC-I and ERK5 expression. MHC-I expression is lower in ρ° cells than in the parental cell lines, but they were equally sensitive to CTL. On the contrary, ρ° cells were more sensitive to activated NK cells than parental cells. On the other hand, L929dt cells were resistant to CTL and NK cells, showed reduced viability when forced to perform OXPHOS, and surviving cells increased MHC-I expression and became sensitive to CTL. The present results suggest that when the reduction in MHC-I levels in tumor cells due to glycolytic metabolism is partial, the increase in sensitivity to NK cells seems to predominate. However, when tumor cells completely lose MHC-I expression, the combination of treatments that increase OXPHOS with CTL-mediated immunotherapy could be a promising therapeutic approach.

No abstract

Our results indicate that NK cells from the synovium of patients with OA, which present an immunoregulatory non-cytotoxic phenotype, show different phenotype comparing with NK cells from peripheral blood, especially expressing granzyme A, a pro-inflammatory molecule which may contribute to the establishment of chronic articular inflammation in this type of patients.

Oxygen depletion and CO 2 formation were measured using a closed system method at various temperatures. No CO 2 inhibition effect was observed. Respiration rates were related to O 2 concentration by a simple Michaelis-Menten equation. Lineweaver-Burk plots of respiratory rate versus O 2 concentration were nonlinear over the whole O 2 concentration range explored. However, this type of analysis allowed us to differentiate two O 2 concentration intervals (above and below 10%) in which the double reciprocal plots are linear. Respiration rates decreased with decreasing temperature following the Arrhenius law. The Michaelis-Menten equation constants V m and K m for the 3 cultivars at 2, 5, and 20°C are tabulated.

A simple mathematical model has been applied to estimate the optimal conditions for modified atmosphere packaging (MAP) of Burlat cherries. The model describes gas exchange in flexible packages, taking into account the respiration rate of the fruit and the transmission rate of gases through the film. The model predicts the evolution of the gas composition inside the package at different conditions. To verify experimentally the model estimations, Burlat cherries were packaged in air and in 3 mixtures of gases at 2 temperatures using 3 different films. Experimental results agree satisfactorily with the predicted values if the O 2 concentration is higher than 2 %.