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The Role of Oncogenes and Redox Signaling in the Regulation of PD-L1 in Cancer

Authors :
Christophe Glorieux
Xiaojun Xia
Peng Huang
Source :
Cancers, Vol 13, Iss 17, p 4426 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

Tumor cells can evade the immune system via multiple mechanisms, including the dysregulation of the immune checkpoint signaling. These signaling molecules are important factors that can either stimulate or inhibit tumor immune response. Under normal physiological conditions, the interaction between programmed cell death ligand 1 (PD-L1) and its receptor, programmed cell death 1 (PD-1), negatively regulates T cell function. In cancer cells, high expression of PD-L1 plays a key role in cancer evasion of the immune surveillance and seems to be correlated with clinical response to immunotherapy. As such, it is important to understand various mechanisms by which PD-L1 is regulated. In this review article, we provide an up-to-date review of the different mechanisms that regulate PD-L1 expression in cancer. We will focus on the roles of oncogenic signals (c-Myc, EML4-ALK, K-ras and p53 mutants), growth factor receptors (EGFR and FGFR), and redox signaling in the regulation of PD-L1 expression and discuss their clinical relevance and therapeutic implications. These oncogenic signalings have common and distinct regulatory mechanisms and can also cooperatively control tumor PD-L1 expression. Finally, strategies to target PD-L1 expression in tumor microenvironment including combination therapies will be also discussed.

Details

Language :
English
ISSN :
20726694
Volume :
13
Issue :
17
Database :
Directory of Open Access Journals
Journal :
Cancers
Publication Type :
Academic Journal
Accession number :
edsdoj.4e8ffc840ed3401588c362d37bb46867
Document Type :
article
Full Text :
https://doi.org/10.3390/cancers13174426