Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
Departments of Urology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
Hum Pathol. 2020 Jul;101:31-39. doi: 10.1016/j.humpath.2020.04.003. Epub 2020 Apr 30.
Renal cell carcinoma (RCC) with sarcomatoid changes and rhabdoid features has shown poor outcomes. Several immune checkpoint inhibitors including programmed cell death protein 1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors have been approved for the treatment of RCC. Combination therapy using PD-1/PD-L1 and indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors has also been used to treat various malignancies. However, little is known about IDO1 expression and therapeutic effects of the IDO1 inhibitor in RCC. Herein, we retrospectively analyzed the expression of PD-L1/IDO1 and examined its relationship with tumor-infiltrating lymphocyte (TIL) status and prognostic effect. We investigated the PD-L1, IDO1, CD3, CD4, and CD8 immunoexpression status in 60 cases of sarcomatoid/rhabdoid RCC. The PD-L1 and IDO1 results were defined by the tumor proportion score. For the evaluation of TIL status, we counted the number of lymphocytes located in the tumor and averaged the numbers over five high-power fields for each case. The results revealed PD-L1 and IDO1 expression was observed more frequently in the sarcomatoid/rhabdoid component than in the nonsarcomatoid/nonrhabdoid component. The correlation between PD-L1 and IDO1 expression was significant (P = 0.0076). PD-L1 expression and coexpression of PD-L1 and IDO1 were correlated with a high density of CD3, CD4, and CD8 T cells. There was no significant difference in overall survival among the patients with PD-L1 and/or IDO1 expression, but PD-L1 expression and coexpression were related to poor progression-free survival. Our results suggest that combination therapy using the PD-1/PD-L1 inhibitor and IDO1 inhibitor may be effective for treating sarcomatoid/rhabdoid RCC.
肾细胞癌（RCC）伴肉瘤样和横纹肌样改变的患者预后较差。几种免疫检查点抑制剂，包括程序性细胞死亡蛋白 1（PD-1）/程序性死亡配体 1（PD-L1）抑制剂，已被批准用于治疗 RCC。PD-1/PD-L1 和吲哚胺 2,3-双加氧酶 1（IDO1）抑制剂联合治疗也已用于治疗各种恶性肿瘤。然而，关于 IDO1 表达及其在 RCC 中的治疗效果知之甚少。在此，我们回顾性分析了 PD-L1/IDO1 的表达，并研究了其与肿瘤浸润淋巴细胞（TIL）状态和预后的关系。我们研究了 60 例肉瘤样/横纹肌样 RCC 中 PD-L1、IDO1、CD3、CD4 和 CD8 的免疫表达状态。PD-L1 和 IDO1 的结果通过肿瘤比例评分定义。为了评估 TIL 状态，我们计算了位于肿瘤中的淋巴细胞数量，并为每个病例的五个高倍视野平均数量。结果显示，肉瘤样/横纹肌样成分中 PD-L1 和 IDO1 的表达比非肉瘤样/非横纹肌样成分更频繁。PD-L1 和 IDO1 表达之间存在显著相关性（P=0.0076）。PD-L1 表达和 PD-L1 和 IDO1 的共表达与 CD3、CD4 和 CD8 T 细胞的高密度相关。在 PD-L1 和/或 IDO1 表达的患者中，总生存期无显著差异，但 PD-L1 表达和共表达与无进展生存期差相关。我们的结果表明，PD-1/PD-L1 抑制剂和 IDO1 抑制剂联合治疗可能对治疗肉瘤样/横纹肌样 RCC 有效。
