PD-1/PD-L1 expression profiles within intrahepatic cholangiocarcinoma predict clinical outcome
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(2020) 18:303
RESEARCH
Open Access
PD-1/PD-L1 expression profiles within intrahepatic cholangiocarcinoma predict clinical outcome Lingyu Tian1†, Jiaqiang Ma1†, Lijie Ma2†, Bohao Zheng3, Longzi Liu4, Danjun Song1, Yining Wang1, Zhao Zhang5, Qiang Gao1, Kang Song1* and Xiaoying Wang1*
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-1High within CD8+ PD-1+ T cells significantly correlated with advanced TNM stage (P = 0.035). ICC patients with high proportion of CD8+ PD-1High 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-1High (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-1High T cells may cooperatively play a role in inhibiting anti-tumor immunity. Conclusion: CD68+ PD-L1+ macrophages and CD8+ PD-1High T cells predict unfavorable prognosis, which could also bring new progress about immune target therapy in ICC research. Keywords: Intrahepatic cholangiocarcinoma, Programmed cell death protein-1, Programmed cell death protein ligand 1, Immunotherapy, Tumor immune micro-environment
Synopsis This research addressed the prognostic value of PD-1/PDL1 expression on CD8+ T cells and CD68+ macrophages in intrahepatic cholangiocarcinoma. The CD68+ PD-L1+ macrophages and CD8+ PD-1High T cells may cooperatively play a role in inhibiting anti-tumor immunity. * Correspondence: [email protected]; [email protected] † Lingyu Tian, Jiaqiang Ma and Lijie Ma contributed equally to this work. 1 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 Full list of author information is available at the end of the article
Immune target therapy may bring better oncological outcomes for ICC patients.
Introduction Intrahepatic cholangiocarcinoma (ICC), a highly aggressive biliary epithelial malignancy, roughly accounts for 10–15% of primary liver cancer, with an increasing disease morbidity and mortality worldwide [1, 2]. Risk factors of ICC mainly include cholangitis, biliary cirrhosis, hepatolithiasis, and viral hepatitis B/C, i
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