Interestingly, Escuredo found that 81% of renal cell carcinoma lost the PlexinB1 expression [44]; although Zuazo-Gaztelu et al. found that the treatment of anti-SEMA4D antibody could decrease tumor proliferative activity and extend the life span of mice, an unexpected increase in tumor metastasis was observed, and they found that the number of macrophages with positive SEMA4D expression increased significantly after treatment and may promote cancer progression through increased release of SDF1/CXCL12 [37]. This evidence concerns the gene CXCL12 and hereditary clear cell renal cell carcinoma.