CD155 immunohistochemical expression in upper tract urothelial carcinoma predicts poor prognosis

A novel immune checkpoint, CD155/T-cell immunoreceptor with Ig and ITIM domains, has been recognized as a new therapeutic target in addition to conventional immune checkpoints, such as anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-L1), for urothelial carcinoma (UC). Fibroblast growth factor receptor (FGFR) is considered another new therapeutic target for UC. As FGFR3-mutant UC may be associated with decreased T-cell infiltration, FGFR3 inhibition may facilitate lymphocyte invasion into the tumor microenvironment. Although a combined effect of immune checkpoint inhibitors and FGFR inhibition is expected, the combined expression profiles of CD155, PD-L1 and FGFR3 have not been evaluated in upper tract UC (UTUC). The present study aimed to investigate the association between CD155 expression and clinicopathological factors in 208 patients with UTUC undergoing radical nephroureterectomy. Furthermore, the expression profiles of CD155, PD-L1 and FGFR3 were compared. Immunohistochemical analysis was performed using tissue microarray specimens and survival analyses were performed using the Kaplan-Meier method and the Cox proportional hazards model. High immunohistochemical expression of CD155 was observed in 177 patients (85.1%) and it was associated with advanced pathological stage and lymphovascular invasion. The survival rate was lower among patients with tumors exhibiting high CD155 expression than among those with tumors with low CD155 expression. In addition, multivariate survival analysis revealed that high CD155 expression was an independent prognostic factor for recurrence (hazard ratio=7.32, 95% CI=1.01-53.35, P=0.049). FGFR3 and immune checkpoint signaling molecules, such as CD155 and PD-L1, had a weak negative correlation. The present results indicated that the expression of CD155 is a useful marker for predicting the recurrence of UTUC. In addition, the immunohistochemical expression profiles of CD155, PD-L1 and FGFR3 may further the understanding of the role of FGFR-targeted therapies in immunotherapy for UTUC.