Intratumoral FOXP3+VEGFR2+ regulatory T cells are predictive markers for recurrence and survival in patients with colorectal cancer

Previously, we have shown that CD8+T/FOXP3+ cell ratio but not FOXP3+ cell number alone is an independent prognostic factor for colorectal cancer. In the present study, we evaluated whether the number of intratumoral FOXP3+VEGFR2+ (itFOXP3+VEGFR2+) T cells alone could be a predictive factor for survival prognosis in patients with colorectal cancer. Distribution of regulatory T cells (Tregs) at tumor sites derived from 88 patients with primary colorectal cancer was fluorescence-immunohistochemically examined. Relatively low number of itFOXP3+VEGFR2+ cells significantly correlated with poor disease-free survival (DS) and overall survival (OS); multivariate analysis indicated that number of itFOXP3+VEGFR2+ cells is an independent predictive and prognostic factor of DS and OS while neither intratumoral FOXP3+ cell number nor intratumoral FOXP3+VEGFR2− cell number alone showed significant correlation with DS or OS. These results suggest that FOXP3+VEGFR2+ may be a better predictive Treg marker than FOXP3+ alone for recurrence and survival in patients with colorectal cancer.

► VEGFR2+ regulatory T cells (Tregs) are selectively expressed by FOXP3high Treg. ► FOXP3+ Treg number alone has not been a predictive factor for survival. ► Relatively low numbers of FOXP3+VEGFR2+ Tregs are associated with poor survival. ► FOXP3+VEGFR2+ may be a better predictive Treg marker in colorectal cancer.