Regulatory tumor-infiltrating lymphocytes prevail in endometrial tumors with low vascular survival ability

Angiogenic activity and vascular survival ability are two distinct vasculature related tumor features that can be assessed in tumor tissues. We examined their correlation with anti-tumor immunity in a series of endometrial carcinomas.

Thirty-three, stage I, endometrial carcinomas of endometrioid histology were analyzed with immunohistochemistry for the expression of CD31 pan-endothelial cell marker and CD25 and FOXP3 markers of regulatory T-cells. Angiogenic activity (AA) was assessed as the microvessel density in the invading tumor front (MVDt1). The vascular survival ability VSA was assessed by comparing the MVDt1 to the MVD in inner tumor areas (MVDt2 and MVDt3). The tumor-infiltrating lymphocyte TIL-density and the CD25+ and FOXP3+ TILD-density were assessed in the invading front and internal tumor areas.

The AA and VSA varied 4-fold and 10-fold among tumors, respectively. Highly angiogenic tumors were more frequently related with high histological grade (p = 0.01) and low VSA (p < 0.05). Although TIL-density was not associated with MVDt1, a statistically significant inverse association was noted with MVDt3 and VSA (p = 0.0005 and p = 0.002, respectively). Similarly, we observed a statistically significant association between the density of regulatory CD25+ and FOXP3+ TILs with low MVDt3 and low VSA (p = 0.03 and p = 0.04, respectively).

Low vascular survival ability relates to high accumulation of regulatory T-cells in inner tumor areas of endometrial carcinomas. The current data hypothesizes meaningful interactions between vascular survival, microenvironmental conditions, and immunosuppression in endometrial cancer.