PD-1/PD-L1 expression profiles within intrahepatic cholangiocarcinoma predict clinical outcome

• Published in: World journal of surgical oncology 2020-11, Vol.18 (1), p.303, Article 303
• Main Authors: Tian, Lingyu, Ma, Jiaqiang, Ma, Lijie, Zheng, Bohao, Liu, Longzi, Song, Danjun, Wang, Yining, Zhang, Zhao, Gao, Qiang, Song, Kang, Wang, Xiaoying
• Format: Article
• Language: English
• Subjects: Apoptosis; B7-H1 Antigen; Bile Duct Neoplasms; Binding sites; Cancer therapies; CD8 antigen; CD8-Positive T-Lymphocytes; Cell death; Cellular proteins; Cholangiocarcinoma; Clinical outcomes; Data collection; Density; Gene expression; Health aspects; Humans; Immunohistochemistry; Immunotherapy; Ligands; Liver cancer; Lymphatic system; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating; Macrophages; Medical prognosis; Metastasis; Methods; Patient outcomes; PD-1 protein; PD-L1 protein; Prognosis; Programmed Cell Death 1 Receptor; Proteins; Risk analysis; Risk factors; Software; Solid tumors; Statistical analysis; Surgery; Tumors
• ISSN: 1477-7819; 1477-7819
• 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.