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Möller, Katharina; Fraune, Christoph; Blessin, Niclas C.; Lennartz, Maximilian; Kluth, Martina; Hube-Magg, Claudia; Lindhorst, Linnea; Dahlem, Roland; Fisch, Margit; Eichenauer, Till; Riechardt, Silke; Simon, Ronald; Sauter, Guido; Büscheck, Franziska; Höppner, Wolfgang; Matthies, Cord; Doh, Ousman; Krech, Till; Marx, Andreas H.; Zecha, Henrik; Rink, Michael; Steurer, Stefan; Clauditz, Till S.

Tumor cell PD-L1 expression is a strong predictor of unfavorable prognosis in immune checkpoint therapy-naive clear cell renal cell cancer

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  • Media type: E-Article
  • Title: Tumor cell PD-L1 expression is a strong predictor of unfavorable prognosis in immune checkpoint therapy-naive clear cell renal cell cancer
  • Contributor: Möller, Katharina; Fraune, Christoph; Blessin, Niclas C.; Lennartz, Maximilian; Kluth, Martina; Hube-Magg, Claudia; Lindhorst, Linnea; Dahlem, Roland; Fisch, Margit; Eichenauer, Till; Riechardt, Silke; Simon, Ronald; Sauter, Guido; Büscheck, Franziska; Höppner, Wolfgang; Matthies, Cord; Doh, Ousman; Krech, Till; Marx, Andreas H.; Zecha, Henrik; Rink, Michael; Steurer, Stefan; Clauditz, Till S.
  • imprint: Springer Science and Business Media LLC, 2021
  • Published in: International Urology and Nephrology
  • Language: English
  • DOI: 10.1007/s11255-021-02841-7
  • ISSN: 0301-1623; 1573-2584
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>PD-L1 expression predicts response to immune checkpoint inhibitors in renal cell carcinomas (RCC), but has also been suggested to be linked to poor patient outcome.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>We analyzed PD-L1 in &gt; 1400 RCC in a tissue microarray format by immunohistochemistry. Results were compared with histological tumor type, parameters of cancer aggressiveness, and intratumoral CD8<jats:sup>+</jats:sup> cytotoxic cells.</jats:p> </jats:sec><jats:sec> <jats:title>Result</jats:title> <jats:p>At a cut-off level of 5% PD-L1 positive tumor cells, PD-L1 positivity was seen in 6.3% of 633 clear cell RCC (ccRCC), 18.2% of 165 papillary RCC, 18.8% of 64 chromophobe RCC, and 41.7% of 103 oncocytomas. In ccRCC, PD-L1 positivity was significantly linked to high ISUP (<jats:italic>p</jats:italic> &lt; 0.0001), Fuhrman (<jats:italic>p</jats:italic> &lt; 0.0001), Thoenes grade (<jats:italic>p</jats:italic> &lt; 0.0001), distant metastasis (<jats:italic>p</jats:italic> = 0.0042), short recurrence-free (<jats:italic>p</jats:italic> &lt; 0.0001), and overall survival (<jats:italic>p</jats:italic> = 0.0002). Intratumoral CD8<jats:sup>+</jats:sup> lymphocytes were more frequent in PD-L1 positive (1055 ± 109) than in PD-L1 negative ccRCC (407 ± 28; <jats:italic>p</jats:italic> &lt; 0.0001). PD-L positive immune cells were seen in 8.2% of all RCC and 13.9% of papillary RCC. In ccRCC, PD-L1 positive immune cells were linked to high numbers of tumor-infiltrating CD8<jats:sup>+</jats:sup> cells (<jats:italic>p</jats:italic> &lt; 0.0001), high ISUP (<jats:italic>p</jats:italic> &lt; 0.0001), Fuhrman (<jats:italic>p</jats:italic> = 0.0027), and Thoenes grade (<jats:italic>p</jats:italic> &lt; 0.0001), and poor tumor-specific survival (<jats:italic>p</jats:italic> = 0.0280).</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>These data suggest that PD-L1 expression in highly immunogenic RCCs facilitates immune evasion and contributes to cancer aggressiveness.</jats:p> </jats:sec>