• Kosuke Ueda, Shigetaka Suekane, Hirofumi Kurose, Katsuaki Chikui, Makoto Nakiri, Kiyoaki Nishihara, Mitsunori Matsuo, Akihiko Kawahara, Hirohisa Yano, and Tsukasa Igawa.
• Department of Urology, Kurume University School of Medicine, Kurume, Japan. Electronic address: ueda_kousuke@med.kurume-u.ac.jp.
• Urol. Oncol. 2018 Nov 1; 36 (11): 499.e9-499.e16.

ObjectiveIn renal cell carcinoma (RCC), several prognostic biomarkers have been identified and are under investigation. Several reports have shown that the expression of programmed death 1 (PD-1) and its ligand PD-L1 is associated with poor outcome for patients with RCC. The present study is aimed at evaluating the expression of PD-1 and PD-L1 and to investigate their clinical and prognostic significance in patients with clear cell RCC (CCRCC) having received molecular targeted therapies. In addition, we also evaluated the relationship between the expression of PD-1 and PD-L1 and intratumoral tumor infiltrating lymphocytes (TILs).MethodsA total of 33 patients with metastatic CCRCC who underwent surgery and received molecular targeted therapies from March 2008 to April 2016 were retrospectively reviewed and analyzed. Tissue specimens from the patients were analyzed for PD-1 and PD-L1 expression by immunohistochemistry.ResultsThe median patient age was 64 years old (range=53-78). The majority of patients were male (81.8%). All Memorial Sloan Kettering Cancer Center risk groups were represented among the patients with 39.4% with favorable-, 51.5% with intermediate- and 9.1% with poor-risk. The expression of PD-1 and PD-L1 was observed in 16 (48.5%) and 9 (27.3%) patients, respectively. The expression of PD-1 and PD-L1 was associated with a larger primary renal tumor size, higher nuclear grade and sarcomatoid feature. Kaplan-Meier analysis revealed that no significant difference in progression free survival of first line molecular targeted therapy was found for PD-1 (P=0.2396) and PD-L1 (P=0.5919) expression. However, PD-1 expression has a significant worse impact on overall survival (OS) (P=0.0385), while for PD-L1 expression only a trend is seen for OS (P=0.1542). The patients with PD-1 and PD-L1 expression showed higher infiltration of CD4 (P<0.0001 and P<0.0001, respectively), CD8 (P=0.0328 and P=0.0044, respectively) and FOXP3 (P<0.0001 and P=0.0033, respectively) positive TILs.ConclusionPD-1 and PD-L1 expression is significantly associated with adverse clinicopathological features in CCRCC. Furthermore, PD-1 expression could be one of the biomarkers suggesting poor outcome in patients with metastatic CCRCC receiving molecular targeted therapies.Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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