Furthermore, most of the remaining clones recognizing HCT116 failed to lyse Colo60H. Several reasons may explain this finding. Colo60H is generally a poorer target than HCT116 ; this may for example be contributable to a higher intrinsic resistance towards CTLs. Moreover, surface expression levels of HLA-A2 may differ; but in FACS-analysis we found very similar HLA-A2 expression of the two CRC cell lines. Finally, differences in the levels of either MSH3 protein expression or of -antigen presentation between HCT116 and Colo60H might be a plausible explanation for this observation. This is an interesting question which shall be addressed in future studies. In summary, the data presented here suggest that the MSH3 frameshift constitutes – from an immunological point of view – one of the major molecular alterations that take place in MSI+ tumors. However, our data are to some extent in conflict to the findings of a pioneer work performed by Williams and colleagues. They very recently analyzed the sensitivity of MSI-induced frameshift mutations towards nonsense mediated RNA decay and found MSH3 to be decay-sensitive. This finding has two major aspects. First, when MSH3 mRNA is degraded very fast, our observed sensitivity of endogenously MSH3 expressing tumor cells towards specific T cells implies that the described epitopes must be very immunogenic and the raised T cells must be of high avidity. Contrary to that it would secondly raise concerns about the potential of MSH3 protein to be cross-presented by professional antigen-presenting cells and thus would substantially limit it’s usefulness as MSI-specific tumor antigen. We here want to bring forward several arguments in favour of the highly immunogenic character of MSH3. A weaker argument would be that all the T cell epitopes derived from cMS that have been described so far are predicted to be sensitive for nonsense-mediated RNA decay. All of these epitopes were found to be naturally presented and specific T cells could efficiently kill tumor cells endogenously expressing the underlying mutation. Then again, both T cell as well as antibody responses specific for cMSI-induced frameshift antigens have been observed in patients as well as healthy HNPCC mutation carriers. A major obstacle of immunotherapy as a whole is the obvious fact, that a tumor mass – a large and heterogeneous ensemble of genetically unstable cells – uses different mechanisms that will possibly allow at least some tumor cells to survive the highly specific immune attack that can be induced by a single T-cell epitope. In this regard, strategies based on the combination of multi-epitope immunotherapeutic approaches with standard therapies may SU5416 abmole finally be clinically most effective. Ambient particles are known as both initiators and enhancers of the clinical manifestations of both allergic and non-allergic airway disease in industrialized countries, and diesel exhaust particles are one of main components of ambient particles. DEP exposure can induce acute irritation of the eyes and throat, lightheadedness, and nausea. Further, they have been associated with the worsening of respiratory symptoms, such as cough, phlegm, chronic bronchitis, and asthma.