Tumor cell PD-L1 expression is a strong predictor of unfavorable prognosis in immune checkpoint therapy-naive clear cell renal cell cancer
Katharina Möller, Christoph Fraune, Niclas C. Blessin, Maximilian Lennartz, Martina Kluth, Claudia Hube‐Magg, Linnea Lindhorst, Roland Dahlem, Margit Fisch, Till Eichenauer, Silke Riechardt, Ronald Simon, Guido Sauter, Franziska Büscheck, Wolfgang Höppner, Cord Matthies, Ousman Doh, Till Krech, Andreas H. Marx, Henrik Zecha, Michael Rink, Stefan Steurer, Till S. Clauditz
Abstract
Abstract Background 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. Methods We analyzed PD-L1 in > 1400 RCC in a tissue microarray format by immunohistochemistry. Results were compared with histological tumor type, parameters of cancer aggressiveness, and intratumoral CD8 + cytotoxic cells. Result 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 ( p < 0.0001), Fuhrman ( p < 0.0001), Thoenes grade ( p < 0.0001), distant metastasis ( p = 0.0042), short recurrence-free ( p < 0.0001), and overall survival ( p = 0.0002). Intratumoral CD8 + lymphocytes were more frequent in PD-L1 positive (1055 ± 109) than in PD-L1 negative ccRCC (407 ± 28; p < 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 + cells ( p < 0.0001), high ISUP ( p < 0.0001), Fuhrman ( p = 0.0027), and Thoenes grade ( p < 0.0001), and poor tumor-specific survival ( p = 0.0280). Conclusions These data suggest that PD-L1 expression in highly immunogenic RCCs facilitates immune evasion and contributes to cancer aggressiveness.