肿瘤细胞 PD-L1 表达是免疫检查点治疗初治透明细胞肾细胞癌不良预后的强预测因子。
Tumor cell PD-L1 expression is a strong predictor of unfavorable prognosis in immune checkpoint therapy-naive clear cell renal cell cancer.
机构信息
Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
出版信息
Int Urol Nephrol. 2021 Dec;53(12):2493-2503. doi: 10.1007/s11255-021-02841-7. Epub 2021 Apr 1.
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.
背景
PD-L1 表达可预测肾细胞癌（RCC）对免疫检查点抑制剂的反应，但也有研究表明其与患者预后不良有关。
方法
我们通过免疫组织化学方法在组织微阵列中分析了超过 1400 例 RCC 中的 PD-L1。结果与组织学肿瘤类型、癌症侵袭性参数和肿瘤内 CD8 细胞毒性细胞进行了比较。
结果
在 5%的 PD-L1 阳性肿瘤细胞截断水平下，在 633 例透明细胞 RCC（ccRCC）中，18.2%的乳头状 RCC、18.8%的嫌色细胞 RCC 和 41.7%的嗜酸细胞瘤中观察到 PD-L1 阳性。在 ccRCC 中，PD-L1 阳性与高 ISUP（p<0.0001）、Fuhrman（p<0.0001）、Thoenes 分级（p<0.0001）、远处转移（p=0.0042）、无复发生存时间短（p<0.0001）和总生存期（p=0.0002）显著相关。PD-L1 阳性 ccRCC 中的肿瘤内 CD8 淋巴细胞更为频繁（1055±109），而 PD-L1 阴性 ccRCC 中的肿瘤内 CD8 淋巴细胞更为频繁（407±28；p<0.0001）。所有 RCC 中 PD-L 阳性免疫细胞为 8.2%，乳头状 RCC 中 PD-L 阳性免疫细胞为 13.9%。在 ccRCC 中，PD-L1 阳性免疫细胞与肿瘤浸润性 CD8 细胞数量高（p<0.0001）、ISUP 高（p<0.0001）、Fuhrman（p=0.0027）和 Thoenes 分级（p<0.0001）以及肿瘤特异性生存不良（p=0.0280）相关。
结论
这些数据表明，高免疫原性 RCC 中的 PD-L1 表达促进了免疫逃逸并促进了癌症侵袭性。
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