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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02022

PD-L1 distribution and perspective for cancer immunotherapy –blockade, knockdown, or inhibition

 Yilun Wu1, 2, Weiyu Chen2,  Zhi Ping (Gordon) Xu2 and  Wenyi Gu2*
  • 1University of Queensland, Australia
  • 2Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Australia

Cancer immunotherapy involves in blocking the interactions between PD-1/PD-L1 immune checkpoint with antibodies and has shown unprecedented positive outcomes in clinics. Particularly, the PD-L1 antibody therapy has shown the efficiency in blocking membrane PD-L1 and efficacy in treating some advanced solid cancers. However, this therapy has limited effects on many solid tumors, suspecting to be revelent to PD-L1 located in other cellular compartments, where they play additional roles and are associated with poor prognosis. In this review, we highlight the advances of 3 current strategies on PD-1/PD-L1 based immunotherapy, summarize cellular distribution of PD-L1, and review the versatile functions of intracellular PD-L1. The intracellular distribution and function of PD-L1 may indicate why not all antibody blockade is able to fully stop PD-L1 biological functions and effectively inhibit tumor growth. In this regard, gene silencing may have advantages over antibody blockade on suppression of PD-L1 sources and functions. Apart from cancer cells, PD-L1 silencing on host immune cells such as APC and DC can also enhance T cell immunity, leading to tumor clearance. Moreover, the molecular regulation of PD-L1 expression in cells is being elucidated, which helps identify potential therapeutic molecules to target PD-L1 production and improve clinical outcomes. Based on our understandings of PD-L1 distribution, regulation, and function, we prospect that the more effective PD-L1-based cancer immunotherapy will be combination therapies.

Keywords: cancer immunotherapy, PD-1/PD-L1 immune checkpoint, cellular PD-L1 distribution, Gene Silencing, PD-L1 regulation, signalling pathway inhibitor, combination therapy

Received: 20 Nov 2018; Accepted: 09 Aug 2019.

Copyright: © 2019 Wu, Chen, Xu and Gu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Wenyi Gu, Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, 4072, Queensland, Australia, w.gu@uq.edu.au