PD-L1 Distribution and Perspective for Cancer Immunotherapy—Blockade, Knockdown, or Inhibition

Cancer immunotherapy involves blocking the interactions between the PD-1/PD-L1 immune checkpoints with antibodies. This 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 adv...

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Published in:Frontiers in immunology Vol. 10; p. 2022
Main Authors: Wu, Yilun, Chen, Weiyu, Xu, Zhi Ping, Gu, Wenyi
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 27.08.2019
Subjects:
cancer immunotherapy
cellular PD-L1 distribution
gene silencing
Immunology
PD-1/PD-L1 immune checkpoint
PD-L1 regulation
signaling pathway inhibitor
cancer immunotherapy
gene silencing
signaling pathway inhibitor
PD-L1 regulation
combination therapy
PD-1/PD-L1 immune checkpoint
cellular PD-L1 distribution
ISSN:1664-3224, 1664-3224
Online Access:Get full text
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Summary:Cancer immunotherapy involves blocking the interactions between the PD-1/PD-L1 immune checkpoints with antibodies. This 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 carcinoma. However, this therapy has limited effects on many solid tumors, suspecting to be relevant 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.
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Edited by: Anahid Jewett, University of California, Los Angeles, United States
Reviewed by: Zoltan Vereb, University of Szeged, Hungary; Maria Fiammetta Romano, University of Naples Federico II, Italy
This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2019.02022