PD-1/PD-L1 expression profiles within intrahepatic cholangiocarcinoma predict clinical outcome
Lingyu Tian, Jiaqiang Ma, Lijie Ma, Bohao Zheng, Longzi Liu, Danjun Song, Yining Wang, Zhao Zhang, Qiang Gao, Kang Song, Xiaoying Wang
Abstract
Abstract Objective 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). Materials and methods 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. Results We found that high proportion of tumor-infiltrating CD8 + PD-1 High within CD8 + PD-1 + T cells significantly correlated with advanced TNM stage ( P = 0.035). ICC patients with high proportion of CD8 + PD-1 High 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 High ( 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 High T cells may cooperatively play a role in inhibiting anti-tumor immunity. Conclusion CD68 + PD-L1 + macrophages and CD8 + PD-1 High T cells predict unfavorable prognosis, which could also bring new progress about immune target therapy in ICC research.