Loss of PD-L1 (SP-142) expression characterizes renal vein tumor thrombus microenvironment in clear cell renal cell carcinoma

Immunotherapy is a promising tool in the treatment of patients with advancer renal cancer, in particular the blockage of immune checkpoint inhibitors. Clear cell renal cell carcinoma is an example of heterogeneous neoplasm and this particular characteristic is responsible of many therapeutic failures so far. Since variations in the local microenvironment across a tumor may conditionate the effect of this new therapy, a deeper knowledge of this issue seems advisable for any treatment success. We have analyzed the PD-L1 (SP142) expression in three different areas in the tumor and in two areas in the renal vein/caval thrombi in 39 advanced clear cell renal cell carcinomas to determine the extent and potential clinical significance of this regional variability. A statistically significant decrease in PD-L1 expression has been detected between the main tumor and its thrombus faction (p < 0.0001). Also, we have observed a high variability in the PD-L1 positivity across the three different areas of the main tumor tested, with only three cases being uniformly positive in all tested areas. In conclusion, PD-L1 expression display a highly variable distribution in clear cell renal cell carcinomas and this particularity should be kept in mind when selecting the tumor samples to be tested for immunotherapy.