On this basis, we hypothesized that mechanical stress could either affect the expression of cell antigens or induce the expression of stress-inducible BAY 73-4506 molecules such as NKG2D receptor ligands able to prime cytotoxic effector lymphocytes cell functions. In the last years the discovery of immunoreceptors recognizing stress inducible proteins have broadened our knowledge on how the immune system is primed. These observations have fostered our interest in Everolimus controlled stress delivery devices that could elicit a tumor immunogenic phenotype able to evoke an immune response, especially when the tumor has already been edited by cytotoxic lymphocytes. Natural Killer cells are potent cytotoxic lymphocytes able to recognize freshly explanted cancer cells and to spontaneously lyse certain tumor targets. They are regulated by a delicate balance between inhibitory receptors, recognizing self MHC class I molecules, and activating receptors for stressinducible molecules. NK cells have the ability to identify and kill virally infected and malignant cells while sparing normal cells. The NK cells regulation was poorly understood until the late 1980��s when the ����missing self���� hypothesis was proposed. According to this hypothesis, down-regulation of MHC class I molecules during viral infection or malignant transformation triggers NK activation. Here we ask whether the treatment of NK resistant cancer cells by mechanical stress could tip the balance between inhibitory and activating tumor expressing molecules in favour of the latter, leading to NK cell activation. In this work, we used two different procedures to mechanically stress cancer and normal cells under controlled conditions. We compared the biological effects of mechanical stimuli delivered either by a micropump device engineered expressly for this purpose, to the ones delivered by a shock waves pulse equipment. The variation in MHC class I molecules before and after mechanical stress was monitored both by means of Raman spectroscopy ) and by means of cytotoxic measurements. The ultimate goal of our study was to understand if the applied mechanical forces could elicit and/or modulate relevant biological cell features, such as their immunogenicity. Moreover, we explored the possibility to use adoptively mechanical manipulations toswitch a tumor NK cell resistant phenotype into a susceptible one. A very clear picture can be revealed from the variation of secondary structure after employing mechanical stress. It shows the reduction of a-helix secondary structure of amide I band for all the cells with mechanical stress. This trend is not clearly observed in Mel 42a cells for which the spectrum is very noisy.