Radiotherapy is one of the most frequent treatment modalities that has very high antitumor effectiveness. Radiation-induced ionization causes breakage of chemical bonds and oxidation of the molecules in the irradiated cells. The most important effect of radiation in cells are DNA single or double strand breaks, which can lead to cell death, mutations and carcinogenesis. However, also non-irradiated cells, neighbouring the irradiated ones, can be affected. The phenomenon which is known as bystander effect is thought to be the result of received signals from neighbouring irradiated cells. The importance of bystander effect in radiation therapy is increasingly growing. Mainly due to its potentiation of the local tumour response, but also because of the possibility to increase normal tissue damage. Beside its local antitumor effect, radiation can also exert antitumor effectiveness on distant, non-treated tumours, due to the activation of immune response of the organism i.e. abscopal effect of irradiation.
The bystander effect is not fully elucidated, and needs further research. Besides the known mechanisms, which are involved in bystander effect, the upregulation of DNA sensors may also be involved. The question that arises is whether the dying tumour cells can activate the neighbouring tumour cells by the released DNA through the DNA sensors and have the bystander effectiveness. The other way could be the activation of the tumour-residing immune cells that can be activated through the DNA sensors, and exert the bystander effect on tumour cells, or have also the abscopal effect on distant tumours.
The objective of the proposed project is to seek the answers to these questions. Upregulation of DNA sensors can activate the immune response in tumours, and may contribute to bystander and abscopal effects of tumour irradiation. Some research was already done in this area on immune cells, but has not evaluated upregulation of an array of sensors. This is the main objective of our research, which will be extended into research of the DNA sensors upregulation also in tumour cells. If tumour cells are activated, they may contribute to bystander effect by direct cytotoxic effect, or activate the immune cytokines contributing to immune response in tumours. Furthermore, we will try to identify the transport pathways of the DNA fragments between the cells.