Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital and Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
Department of General Surgery, Zhongshan Hospital (South), Shanghai Public Health Clinical Center, Fudan University, Shanghai, 200083, China.
World J Surg Oncol. 2020 Nov 23;18(1):303. doi: 10.1186/s12957-020-02082-5.
Immunotherapy targeting the programmed cell death protein-1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) pathway has been observed to be efficient in several solid tumors. We aim to investigate the prognostic significance of PD-1/PD-L1 expression profile in intrahepatic cholangiocarcinoma (ICC).
We investigated the expression of PD-1, PD-L1, CD8 T cells, and CD68 macrophages in paired tumor and adjacent normal tissues from 322 ICC patients using tyramide signal amplification (TSA)-based multiplexed immunohistochemistry.
We found that high proportion of tumor-infiltrating CD8 PD-1 within CD8 PD-1 T cells significantly correlated with advanced TNM stage (P = 0.035). ICC patients with high proportion of CD8 PD-1 in CD8 PD-1 had worse postoperative survival than low proportion patients (P = 0.0037), which was an independently prognostic factor for OS (P = 0.025,). The density of CD68 PD-L1 significantly and positively correlated with the density of CD8 PD-1 (P < 0.0001, r = 0.5927). The proportion of CD68 PD-L1 within CD68 ICC was the risk factor for OS and TTR but not an independently factor for prognosis. The CD68 PD-L1 macrophages and CD8 PD-1 T cells may cooperatively play a role in inhibiting anti-tumor immunity.
CD68 PD-L1 macrophages and CD8 PD-1 T cells predict unfavorable prognosis, which could also bring new progress about immune target therapy in ICC research.
靶向细胞程序性死亡蛋白-1（PD-1）/细胞程序性死亡蛋白配体 1（PD-L1）通路的免疫疗法已在多种实体肿瘤中显示出疗效。我们旨在研究 PD-1/PD-L1 表达谱在肝内胆管癌（ICC）中的预后意义。
我们使用酪胺信号放大（TSA）-基于多重免疫组织化学方法，研究了 322 例 ICC 患者配对肿瘤和相邻正常组织中 PD-1、PD-L1、CD8 T 细胞和 CD68 巨噬细胞的表达情况。
我们发现，肿瘤浸润性 CD8 PD-1 细胞中 CD8 PD-1 的高比例与较晚的 TNM 分期显著相关（P=0.035）。CD8 PD-1 细胞中 CD8 PD-1 高比例的 ICC 患者术后生存时间较低比例患者差（P=0.0037），这是 OS 的独立预后因素（P=0.025）。CD68 PD-L1 的密度与 CD8 PD-1 的密度显著正相关（P＜0.0001，r=0.5927）。CD68 PD-L1 在 CD68 ICC 中的比例是 OS 和 TTR 的危险因素，但不是独立的预后因素。CD68 PD-L1 巨噬细胞和 CD8 PD-1 T 细胞可能共同抑制抗肿瘤免疫。
CD68 PD-L1 巨噬细胞和 CD8 PD-1 T 细胞预示着不良预后，这也可能为 ICC 免疫治疗研究带来新的进展。
