Ricerc@Sapienza

Recent data support that combining radiation therapy (RT) with immune checkpoint inhibitors (ICI) is a promising approach in cancer patients . To date, programmed death ligand 1 (PD-L1) on tumor cells is the only predictive biomarker validated but, so far, available data do not definitively suggest that PD-L1 expression is required for biologic activity of RT-ICI combinations. RT upregulates PD-L1 in cancer cells as a part of a cancer pro-survival program supposed to provide an additional opportunity for the use of ICI . Notably, whether RT-induced PD-L1 might represent a predictive biomarker of response or might simply mirror an immunosuppressed microenvironment is poorly understood. Despite RT is able to boost the immune activation in some patients for whom additional immunotherapy is supposed to be beneficial, in other cases it activates systemic host responses that contribute to treatment resistance .The fact that many patients early acquire resistance indicate that many potential immune suppressors may lead to cancer cells immune-escape, thus abrogating the radiation-induced priming function. Characterizing the molecular pathways activated in those tumor cells able to survive to RT-induced immunogenic death is consequently expected to deepen our understanding of radiation-associated immune regulation . For this to be achieved, it is necessary to have a global vision of how the immune escape related pathways change during treatment, a condition that would require repeated biopsies clearly not feasible during treatment, strongly impairing the reliability of hypothetical biomarkers in prior to therapy tumor samples as predictive biomarker of response. However, this limit can be overcome by using liquid biopsy, through the accessible and repeatable isolation of circulating tumor cells (CTCs) into the bloodstream. Aim of this proposal is to investigate the effects of RT on the immune escape enabling properties of CTCs in patients treated with RT.