Relationship of B7-H3 expression in tumor cells and tumor vasculature with FOXP3+ regulatory T cells in renal cell carcinoma.

BACKGROUND

B7-H3 (CD276), an immune checkpoint molecule, regulates the tumor-immune microenvironment and controls the aggressiveness of various tumors. Although B7-H3 expression has been associated with the number of tumor-infiltrating FOXP3+ regulatory T cells, little information is available about this association in clear cell renal cell carcinoma (ccRCC).

METHODS

Using 252 consecutive cases of ccRCC, we examined the association of B7-H3 expression in both the tumor cells and tumor vasculature with the number of tumor-infiltrating FOXP3+ cells and assessed whether the effects of B7-H3 expression on survival differ according to FOXP3+ cell number.

RESULTS

High B7-H3 expression was observed in the tumor cells and tumor vasculature in 15% and 54% of ccRCC cases, respectively. High FOXP3+ cell number was positively associated with B7-H3 expression in both the tumor cells (odds ratio [OR] =2.93; =0.0041) and tumor vasculature (OR=2.45; =0.0007). Tumor cell B7-H3 expression was associated with increased disease-specific mortality in high FOXP3+ cell number group (hazard ratio [HR] =2.98; =0.017), but not in low FOXP3+ group (=0.71). Tumor vasculature B7-H3 expression was also associated with increased disease-specific mortality in high FOXP3+ cell number group (HR=4.86; =0.0025), but not in low FOXP3+ group (=0.48).

CONCLUSION

We demonstrate that B7-H3 expression in both tumor cells and the tumor vasculature is positively associated with FOXP3+ cell number. Such expression is also associated with increased mortality in high FOXP3+ cell number group, but not in low FOXP3+ cell number group. These findings suggest that B7-H3-expressing ccRCCs may exert tumor-promoting immunity by interacting with FOXP3+ regulatory T cells in the tumor microenvironment.