Clinic of General, Oncological and Functional Urology, Medical University of Warsaw, Warsaw, Poland.
Department of Pathomorphology, Medical University of Gdansk, Gdańsk, Poland.
Urol Oncol. 2022 May;40(5):200.e1-200.e10. doi: 10.1016/j.urolonc.2022.02.001. Epub 2022 Mar 26.
Renal cell carcinoma (RCC) frequently invades renal vein forming neoplastic thrombus. The expression of immune checkpoint receptors in RCC was addressed in multiple studies, but little is known about the expression and prognostic significance of programmed death ligand-1 in tumor thrombus.
The study aimed to evaluate the expression of PD-L1 within venous tumor thrombus and primary tumor using 2 independent antibody clones (22c3 and E1L3N) and to assess its value in predicting overall survival (OS) in the subgroup of patients with RCC and renal vein thrombus.
Eighty-two patients with RCC and venous tumor thrombus that underwent nephrectomy were enrolled. The expression of PD-L1 was assessed utilizing tissue microarrays separately on tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs). The frequency of PD-L1 expression on TCs and TILs varied between tumor and thrombus compartments and was dependent on the antibody clone used. The expression of PD-L1 on TCs and/or TILs was associated with worse OS irrespectively of the antibody and the analyzed compartment. Nevertheless, the best prognostic performance was noted for the combined assessment of PD-L1 expression on TCs and TILs in venous tumor thrombus with the use of 22c3 antibody. The multivariable Cox regression model predicting OS incorporated PD-L1 22c3 in venous tumor thrombus (hazards ratio [HR] = 3.64, 95% confidence interval [CI] = 1.63-8.14, P = 0.002) and nodal status (HR = 2.88, 95% CI = 1.18-7.03, P = 0.02).
PD-L1 may become a valuable tool for prognostic purposes in this specific subgroup of patients and be incorporated into the respective models qualifying for adjuvant treatment.
肾细胞癌 (RCC) 常侵犯肾静脉形成肿瘤血栓。多项研究探讨了 RCC 中免疫检查点受体的表达,但对于肿瘤血栓中程序性死亡配体-1 的表达及其预后意义知之甚少。
本研究旨在使用 2 种独立的抗体克隆(22c3 和 E1L3N)评估静脉肿瘤血栓和原发肿瘤中 PD-L1 的表达,并评估其在伴有肾静脉血栓的 RCC 患者亚组中预测总生存期(OS)的价值。
共纳入 82 例接受肾切除术的伴有静脉肿瘤血栓的 RCC 患者。利用组织微阵列分别评估肿瘤细胞(TCs)和肿瘤浸润淋巴细胞(TILs)中 PD-L1 的表达。PD-L1 在 TCs 和血栓腔室中的表达存在异质性,且取决于所使用的抗体克隆。TCs 和/或 TILs 中 PD-L1 的表达与 OS 不良相关,而与抗体和分析的腔室无关。然而,使用 22c3 抗体评估静脉肿瘤血栓中 PD-L1 在 TCs 和 TILs 上的联合表达,可获得最佳的预后性能。预测 OS 的多变量 Cox 回归模型纳入了静脉肿瘤血栓中 PD-L1 22c3(危险比 [HR] = 3.64,95%置信区间 [CI] = 1.63-8.14,P = 0.002)和淋巴结状态(HR = 2.88,95% CI = 1.18-7.03,P = 0.02)。
PD-L1 可能成为该特定患者亚组中具有预后意义的有用工具,并纳入相应的辅助治疗资格模型。