Ricerc@Sapienza

The programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) pathway has emerged as a critical inhibitory pathway regulating T-cell response in urological malignancies. Nevertheless, the high degree of non-responders demonstrates that we are still far from completely understand the events underlying tumor immune resistance. Although the expression of PD-L1 in tumor tissue has been correlated with clinical response to anti PD-1 inhibitors, the ability of this marker to discriminate the subgroup of patients who derive benefit from immunotherapy is suboptimal. Circulating tumor cells (CTCs), as an accessible source of tumor for biologic characterization that can be serially obtained with minimally invasive procedure, hold significant promise to facilitate treatment-specific biomarkers discovery. It has been recently demonstrated that the persistence of PD-L1 positive CTCs is indicative for treatment resistance in metastatic chemo-refractory patients. Furthermore, it has been previously suggested that PD-L1 positive CTCs may represent a small population of partial epithelial mesenchymal transition (EMT)-transformed cancer cells. The bidirectional crosstalk between PD-L1 expression and EMT is well described, although the molecular determinants of this association remain incompletely understood. Although only limited data exist, preliminary research suggests that PD-L1 is expressed in CTCs with mesenchymal traits. Basing upon previous observation that the presence of PD-L1 on CTCs apparently predicts resistance to the anti PD-1 nivolumab in metastatic lung cancer patients, we aim to investigate the co-expression of PD-L1 and EMT markers in CTCs from bladder cancer patients, as a possible molecular background of immune escape.