Prognostic value of PD-1 and PD-L1 expression in patients with metastatic clear cell renal cell carcinoma

• Published in: Urologic oncology 2018-11, Vol.36 (11), p.499.e9-499.e16
• Main Authors: Ueda, Kosuke, Suekane, Shigetaka, Kurose, Hirofumi, Chikui, Katsuaki, Nakiri, Makoto, Nishihara, Kiyoaki, Matsuo, Mitsunori, Kawahara, Akihiko, Yano, Hirohisa, Igawa, Tsukasa
• Format: Article
• Language: English
• Subjects: Aged; B7-H1 Antigen - analysis; B7-H1 Antigen - biosynthesis; Biomarkers, Tumor - analysis; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - mortality; Carcinoma, Renal Cell - pathology; Female; Humans; Kaplan-Meier Estimate; Kidney Neoplasms - drug therapy; Kidney Neoplasms - mortality; Kidney Neoplasms - pathology; Lymphocytes, Tumor-Infiltrating - pathology; Male; Middle Aged; Molecular Targeted Therapy; PD-1, PD-L1; Prognosis; Programmed Cell Death 1 Receptor - analysis; Programmed Cell Death 1 Receptor - biosynthesis; Progression-Free Survival; Proportional Hazards Models; Renal cell carcinoma; Retrospective Studies; Tumor infiltrating lymphocytes
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2018.07.003

•We evaluated prognostic value of PD-1 and PD-L1 expression in metastatic RCC.•We also evaluated the relationship between these expression and intratumoral TILs.•PD-1 and PD-L1 expression was associated with adverse clinicopathological feature.•PD-1 and PD-L1 expression was associated with higher infiltration of TILs.•PD-1 expression has a significant worse impact on OS. In 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). A 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. The 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