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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Tumor cell PD-L1 expression is a strong predictor of unfavorable prognosis in immune checkpoint therapy-naive clear cell renal cell cancer. / 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.
In: INT UROL NEPHROL, Vol. 53, No. 12, 12.2021, p. 2493-2503.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Tumor cell PD-L1 expression is a strong predictor of unfavorable prognosis in immune checkpoint therapy-naive clear cell renal cell cancer
AU - Möller, Katharina
AU - Fraune, Christoph
AU - Blessin, Niclas C
AU - Lennartz, Maximilian
AU - Kluth, Martina
AU - Hube-Magg, Claudia
AU - Lindhorst, Linnea
AU - Dahlem, Roland
AU - Fisch, Margit
AU - Eichenauer, Till
AU - Riechardt, Silke
AU - Simon, Ronald
AU - Sauter, Guido
AU - Büscheck, Franziska
AU - Höppner, Wolfgang
AU - Matthies, Cord
AU - Doh, Ousman
AU - Krech, Till
AU - Marx, Andreas H
AU - Zecha, Henrik
AU - Rink, Michael
AU - Steurer, Stefan
AU - Clauditz, Till S
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
U2 - 10.1007/s11255-021-02841-7
DO - 10.1007/s11255-021-02841-7
M3 - SCORING: Journal article
C2 - 33797012
VL - 53
SP - 2493
EP - 2503
JO - INT UROL NEPHROL
JF - INT UROL NEPHROL
SN - 0301-1623
IS - 12
ER -