Background. Vascular endothelial growth factor pathway (VEGF)-tyrosine kinase inhibitors (TKIs) are used as the first-line treatment for patients with metastatic clear cell renal cell carcinoma (mCCRCC). Recently, programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) blockade emerged as promising therapy for renal cell carcinoma. However, the expression pattern and prognostic implication of programmed death-ligands (PD-Ls) in mCCRCC patients receiving VEGF-TKI remain unclear. Patients and Methods. PD-L1 and PD-L2 expression in tumor cells and the quantities of PD-11 tumor-infiltrating lymphocytes were immunohistochemically evaluated in 91 mCCRCC patients treated with VEGF-TKI, and their associations with VEGF-TKI responsiveness and clinical outcome were analyzed. Results. PD-L1 immunopositivity was observed in 17.6% and significantly associated with a high International Society of Urological Pathology grade (p =.031) and sarcomatoid features (p =.014). PD-L2 immunopositivity was observed in 39.6% and was not associated with any of the assessed clinicopathological variables. PD-Ll-positive cases showed poor VEGF-TKI responsiveness (p =.012) compared with PD-Ll-negative cases. In univariate survival analysis, PD-L1 immunopositivity was significantly associated with shorter overall survival (OS) (p =.037) and progression-free survival (PFS) (p =.043). Multivariate survival analysis revealed that PD-L1 expression was independently associated with poor OS (p =.038) and PFS(p =.013) in addition to tumor necrosis (p =.006; p =.029, respectively) and Memorial Sloan Kettering Cancer Center score (p =.018; p =.032, respectively). PD-L2 expression was neither associated with VEGF-TKI responsiveness nor patients’ outcome. Conclusion. PD-L1 expression was significantly related to lack of VEGF-TKI responsiveness and independently associated with shorter survival in mCCRCC patients after VEGF-TKI treatment. PD-L1 may have a predictive and prognostic value for determining the value of VEGF-TKI treatment in patients with mCCRCC.
- Metastatic clear cell renal cell carcinoma
- Programmed death ligand-1
- Programmed death ligand-2
- Vascular endothelial growth factor pathway-tyrosine kinase inhibitor