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Programmed cell death protein-1 (PD-1)/programmed death-ligand-1 (PD-L1) axis in hepatocellular carcinoma: prognostic and therapeutic perspectives

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Abstract

Hepatocellular carcinoma (HCC) is the most common primary neoplasia of the liver. There have been tremendous efforts in the development of therapeutic strategies in the last decades. As opposed to other cancer entities immunotherapy has just recently gained popularity in HCC. Among various immunotherapy approaches, programmed cell death protein-1 (PD-1), and its ligand programmed death receptor ligand-1 (PD-L1) axis became one of the most promising pathway of the decade. The scientific interest in PD-1/PD-L1 axis is definitely justified due to: ability to detect PD-L1 expression in patients that underwent resection for HCC with prognostic values; the role of serum PD-L1 as a tool to identify early recurrences and to monitor treatment outcome; PD-1/PDL1 is a highly targetable pathway, with possible predictive markers, and with high clinical applicability that might help us in selecting a subgroup of HCC patients who are most likely to benefit from PD-1/PD-L1 inhibitors. In this review we will first discuss the prognostic role of PD-1/PD-L1 as a bio-marker in various clinical scenarios. Afterwards we will critically analyse the recently published trials with PD-1/PD-L1 inhibitors in HCC either alone or in combination with other treatment modalities. The higher focus will be on clinical rather than preclinical studies. Nevertheless, the strengths and limits of PD-1/PD-L1 axis in both prognosis and therapy of HCC will be highlighted.

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  1. T. Mocan and Z. Sparchez equally contributed.

Authors and Affiliations

  1. 3rd Medical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, 400012, Cluj, Romania

    T. Mocan, Z. Sparchez, R. Craciun & C. N. Bora

  2. Institute for Gastroenterology and Hepatology, Croitorilor St. 19-21, Cluj-Napoca, 400012, Cluj, Romania

    T. Mocan, Z. Sparchez, R. Craciun & C. N. Bora

  3. Medical Informatics and Biostatistics Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, 400012, Cluj, Romania

    D. C. Leucuta

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Contributions

Tudor Mocan and Zeno Sparchez have equally contributed to this paper with conception and design of the study, literature review, drafting critical revision and editing; Rares Craciun was involved in literature review and drafted Fig. 1; Cristina Nelida Bora performed literature review and drafted the initial version; Daniel Corneliu Leucuta supervised the study and revised the manuscript for important intellectual content; all authors have read and approved the final version to be published.

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Correspondence to T. Mocan.

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Mocan, T., Sparchez, Z., Craciun, R. et al. Programmed cell death protein-1 (PD-1)/programmed death-ligand-1 (PD-L1) axis in hepatocellular carcinoma: prognostic and therapeutic perspectives. Clin Transl Oncol 21, 702–712 (2019). https://doi.org/10.1007/s12094-018-1975-4

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