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.