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

Background

It has not been established whether activation of immune checkpoint pathways is correlated with the clinical course of systemic therapies for metastatic renal cell carcinoma (mRCC), particularly tyrosine kinase inhibitors (TKIs). The objective of this study was to analyze the expression pattern of immune checkpoint-associated molecules in tumor tissues to determine the prognostic significance of these molecules in mRCC patients treated with 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

Twelve patients (19.3%) were revealed to be positive for PD-1-positive TILs, while positive expression of PD-L1 and PD-L2 were detected in 12 (19.3%) and 10 (16.1%) patients, respectively. Patients with positive PDL-L1 expression had significantly unfavorable progression-free survival (PFS) compared with those without positive PD-L1 expression, despite the remaining two molecules having no significant impact on PFS. Additionally, overall survival (OS) 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 prognostic predictors 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 OS.

Conclusions

Positive expression of immune checkpoint-associated molecules in tumor tissues, particularly that of PD-L1, could be useful prognostic indicator in mRCC patients receiving TKIs as first-line systemic therapy.

Clinical trial identification

Legal entity responsible for the study

N/A

Funding

Kobe University

Disclosure

All authors have declared no conflicts of interest.