Expression pattern of immune checkpoint-associated molecules in radical nephrectomy specimens as a prognosticator in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors.

OBJECTIVE: To analyze the expression pattern of immune checkpoint-associated molecules in tumor tissues to determine the prognostic significance of these molecules in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs).

METHODS: Radical nephrectomy specimens were obtained from 62 patients treated with TKIs as first-line systemic therapy for mRCC. The proportions of programmed death-1 (PD-1)-positive tumor infiltrating lymphocytes (TILs) as well as those of tumor cells positive for PD-ligand 1 (PD-L1) and PD-L2 were analyzed by immunohistochemical staining.

RESULTS: Overall, 12 patients (19.3%) were revealed to be positive for PD-1-positive TILs, whereas positive expression of PD-L1 and PD-L2 were detected in 12 (19.3%) and 10 (16.1%) patients, respectively. Patients with positivePDL-L1 expression had significantly unfavorable progression-free survival (PFS) compared with those without positive PD-L1 expression, despite the remaining 2 molecules having no significant effect on PFS. Additionally, overall survival in patients positive for PD-1, PD-L1, or PD-L2 expression was significantly poorer than that in those without expression of each immune checkpoint-associated molecule. Multivariate analyses of several parameters identified the following independent prognosticators after the introduction of TKIs: PD-L1 expression status for PFS and lymph node metastasis, Memorial Sloan-Kettering Cancer Center classification and expression statuses of PD-1-positive TILs, and PD-L1 for overall survival.

CONCLUSIONS: Positive expression of immune checkpoint-associated molecules in tumor tissues could be useful prognosticators in patients with mRCC receiving TKIs as first-line systemic therapy.